Amyloid beta-Protein Precursor: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)Amyloid beta-Peptides: Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.Amyloid: A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.Protein PrecursorsAmyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.Caspase 1: A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2- hydroxyethyl)-4-methylthiazolium chloride.Aprotinin: A single-chain polypeptide derived from bovine tissues consisting of 58 amino-acid residues. It is an inhibitor of proteolytic enzymes including CHYMOTRYPSIN; KALLIKREIN; PLASMIN; and TRYPSIN. It is used in the treatment of HEMORRHAGE associated with raised plasma concentrations of plasmin. It is also used to reduce blood loss and transfusion requirements in patients at high risk of major blood loss during and following open heart surgery with EXTRACORPOREAL CIRCULATION. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Factor XIa: Activated form of factor XI. In the intrinsic pathway, Factor XI is activated to XIa by factor XIIa in the presence of cofactor HMWK; (HIGH MOLECULAR WEIGHT KININOGEN). Factor XIa then activates factor IX to factor IXa in the presence of calcium.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Serum Amyloid A Protein: An ACUTE PHASE REACTION protein present in low concentrations in normal sera, but found at higher concentrations in sera of older persons and in patients with AMYLOIDOSIS. It is the circulating precusor of amyloid A protein, which is found deposited in AA type AMYLOID FIBRILS.Amyloidosis: A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.

The amyloid precursor protein interacts with Go heterotrimeric protein within a cell compartment specialized in signal transduction. (1/2953)

The function of the beta-amyloid protein precursor (betaAPP), a transmembrane molecule involved in Alzheimer pathologies, is poorly understood. We recently reported the presence of a fraction of betaAPP in cholesterol and sphingoglycolipid-enriched microdomains (CSEM), a caveolae-like compartment specialized in signal transduction. To investigate whether betaAPP actually interferes with cell signaling, we reexamined the interaction between betaAPP and Go GTPase. In strong contrast with results obtained with reconstituted phospholipid vesicles (Okamoto et al., 1995), we find that incubating total neuronal membranes with 22C11, an antibody that recognizes an N-terminal betaAPP epitope, reduces high-affinity Go GTPase activity. This inhibition is specific of Galphao and is reproduced, in the absence of 22C11, by the addition of the betaAPP C-terminal domain but not by two distinct mutated betaAPP C-terminal domains that do not bind Galphao. This inhibition of Galphao GTPase activity by either 22C11 or wild-type betaAPP cytoplasmic domain suggests that intracellular interactions between betaAPP and Galphao could be regulated by extracellular signals. To verify whether this interaction is preserved in CSEM, we first used biochemical, immunocytochemical, and ultrastructural techniques to unambiguously confirm the colocalization of Galphao and betaAPP in CSEM. We show that inhibition of basal Galphao GTPase activity also occurs within CSEM and correlates with the coimmunoprecipitation of Galphao and betaAPP. The regulation of Galphao GTPase activity by betaAPP in a compartment specialized in signaling may have important consequences for our understanding of the physiopathological functions of betaAPP.  (+info)

Proteolytic processing of the Alzheimer's disease amyloid precursor protein within its cytoplasmic domain by caspase-like proteases. (2/2953)

Alzheimer's disease is characterized by neurodegeneration and deposition of betaA4, a peptide that is proteolytically released from the amyloid precursor protein (APP). Missense mutations in the genes coding for APP and for the polytopic membrane proteins presenilin (PS) 1 and PS2 have been linked to familial forms of early-onset Alzheimer's disease. Overexpression of presenilins, especially that of PS2, induces increased susceptibility for apoptosis that is even more pronounced in cells expressing presenilin mutants. Additionally, presenilins themselves are targets for activated caspases in apoptotic cells. When we analyzed APP in COS-7 cells overexpressing PS2, we observed proteolytic processing close to the APP carboxyl terminus. Proteolytic conversion was increased in the presence of PS2-I, which encodes one of the known PS2 pathogenic mutations. The same proteolytic processing occurred in cells treated with chemical inducers of apoptosis, suggesting a participation of activated caspases in the carboxyl-terminal truncation of APP. This was confirmed by showing that specific caspase inhibitors blocked the apoptotic conversion of APP. Sequence analysis of the APP cytosolic domain revealed a consensus motif for group III caspases ((IVL)ExD). Mutation of the corresponding Asp664 residue abolished cleavage, thereby identifying APP as a target molecule for caspase-like proteases in the pathways of programmed cellular death.  (+info)

Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5'-untranslated region sequences. (3/2953)

The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-1 (IL-1) in microglia in affected areas of the AD brain. Here we demonstrate that IL-1alpha and IL-1beta increase APP synthesis by up to 6-fold in primary human astrocytes and by 15-fold in human astrocytoma cells without changing the steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 5'-untranslated region (5'-UTR) conferred translational regulation by IL-1alpha and IL-1beta to a chloramphenicol acetyltransferase (CAT) reporter gene. Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas both base-line and IL-1-dependent CAT protein synthesis were increased. This APP mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap site and is homologous to related translational control elements in the 5'-UTR of the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides a mechanism by which IL-1 influences the pathogenesis of AD.  (+info)

Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. (4/2953)

Transgenic mice overexpressing different forms of amyloid precursor protein (APP), i.e. wild type or clinical mutants, displayed an essentially comparable early phenotype in terms of behavior, differential glutamatergic responses, deficits in maintenance of long term potentiation, and premature death. The cognitive impairment, demonstrated in F1 hybrids of the different APP transgenic lines, was significantly different from nontransgenic littermates as early as 3 months of age. Biochemical analysis of secreted and membrane-bound APP, C-terminal "stubs," and Abeta(40) and Abeta(42) peptides in brain indicated that no single intermediate can be responsible for the complex of phenotypic dysfunctions. As expected, the Abeta(42) levels were most prominent in APP/London transgenic mice and correlated directly with the formation of amyloid plaques in older mice of this line. Plaques were associated with immunoreactivity for hyperphosphorylated tau, eventually signaling some form of tau pathology. In conclusion, the different APP transgenic mouse lines studied display cognitive deficits and phenotypic traits early in life that dissociated in time from the formation of amyloid plaques and will be good models for both early and late neuropathological and clinical aspects of Alzheimer's disease.  (+info)

Amyloid precursor protein metabolism in fibroblasts from individuals with one, two or three copies of the amyloid precursor protein (APP) gene. (5/2953)

Protein kinase C (PKC)-activated modulation of amyloid precursor protein (APP) metabolism has been investigated in natural models of altered APP expression due to the presence of one, two or three copies of the APP gene. We show that levels of APP present in human skin fibroblasts strongly influence the effect of PKC activation of soluble APP (sAPP) release. Thus fibroblasts derived from a patient with a deletion in chromosome 21 including the APP locus (Delta21) had lower levels of both APP mRNA and cell-associated APP, and showed an exaggerated phorbol-ester-induced sAPP release, when compared with fibroblasts from control individuals. In contrast, fibroblasts from chromosome 21 trisomic Down's syndrome patients failed to show a concentration-dependent response to phorbol ester treatment. These results suggest that the levels of APP expression can affect the degree of response to PKC-mediated modulation of the metabolism of this protein.  (+info)

Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor-binding protein. (6/2953)

The principal component of Alzheimer's amyloid plaques, Abeta, derives from proteolytic processing of the Alzheimer's amyloid protein precursor (APP). FE65 is a brain-enriched protein that binds to APP. Although several laboratories have characterized the APP-FE65 interaction in vitro, the possible relevance of this interaction to Alzheimer's disease has remained unclear. We demonstrate here that APP and FE65 co-localize in the endoplasmic reticulum/Golgi and possibly in endosomes. Moreover, FE65 increases translocation of APP to the cell surface, as well as both alphaAPPs and Abeta secretion. The dramatic (4-fold) FE65-dependent increase in Abeta secretion suggests that agents which inhibit the interaction of FE65 with APP might reduce Abeta secretion in the brain and therefore be useful for preventing or slowing amyloid plaque formation.  (+info)

Mechanism of the cleavage specificity of Alzheimer's disease gamma-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. (7/2953)

Proteolytic processing of the amyloid precursor protein by beta-secretase yields A4CT (C99), which is cleaved further by the as yet unknown gamma-secretase, yielding the beta-amyloid (Abeta) peptide with 40 (Abeta40) or 42 residues (Abeta42). Because the position of gamma-secretase cleavage is crucial for the pathogenesis of Alzheimer's disease, we individually replaced all membrane-domain residues of A4CT outside the Abeta domain with phenylalanine, stably transfected the constructs in COS7 cells, and determined the effect of these mutations on the cleavage specificity of gamma-secretase (Abeta42/Abeta40 ratio). Compared with wild-type A4CT, mutations at Val-44, Ile-47, and Val-50 led to decreased Abeta42/Abeta40 ratios, whereas mutations at Thr-43, Ile-45, Val-46, Leu-49, and Met-51 led to increased Abeta42/Abeta40 ratios. A massive effect was observed for I45F (34-fold increase) making this construct important for the generation of animal models for Alzheimer's disease. Unlike the other mutations, A4CT-V44F was processed mainly to Abeta38, as determined by mass spectrometry. Our data provide a detailed model for the active site of gamma-secretase: gamma-secretase interacts with A4CT by binding to one side of the alpha-helical transmembrane domain of A4CT. Mutations in the transmembrane domain of A4CT interfere with the interaction between gamma-secretase and A4CT and, thus, alter the cleavage specificity of gamma-secretase.  (+info)

Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. (8/2953)

Autosomal dominant forms of familial Alzheimer's disease (FAD) are associated with increased production of the amyloid beta peptide, Abeta42, which is derived from the amyloid protein precursor (APP). In FAD, as well as in sporadic forms of the illness, Abeta peptides accumulate abnormally in the brain in the form of amyloid plaques. Here, we show that overexpression of FAD(717V-->F)-mutant human APP in neurons of transgenic mice decreases the density of presynaptic terminals and neurons well before these mice develop amyloid plaques. Electrophysiological recordings from the hippocampus revealed prominent deficits in synaptic transmission, which also preceded amyloid deposition by several months. Although in young mice, functional and structural neuronal deficits were of similar magnitude, functional deficits became predominant with advancing age. Increased Abeta production in the context of decreased overall APP expression, achieved by addition of the Swedish FAD mutation to the APP transgene in a second line of mice, further increased synaptic transmission deficits in young APP mice without plaques. These results suggest a neurotoxic effect of Abeta that is independent of plaque formation.  (+info)

*Amyloid beta

Hiltunen M, van Groen T, Jolkkonen J (2009). "Functional roles of amyloid-beta protein precursor and amyloid-beta peptides: ... and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein). Aβ circulates in plasma, ... The peptides derive from the amyloid precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield A ... Amyloid beta can be measured semiquantitatively with immunostaining, which also allows one to determine location. Amyloid beta ...

*Amyloid precursor protein

"Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production". Nature. 360 ... a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition". The ... Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause ... between expression of apolipoprotein E and beta-amyloid precursor protein are altered in proximity to Alzheimer beta-amyloid ...

*Alzheimer's disease research

Gamma secretase is a protein complex thought to be a fundamental building block in the development of the amyloid beta peptide ... amyloid protein precursor (APP) was found to be indirectly related based on network analysis. Aβ (one of the diagnostic ... vaccines against amyloid beta. Other approaches are neuroprotective agents, like AL-108 (phase II completed); or metal-protein ... It is believed to reduce the production of the toxic amyloid beta in favor of shorter forms of the peptide. Negative results ...

*Christine Van Broeckhoven

Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis, Science. 1990 June 1;248(4959):1120-2 ... in 1993 she and three other scientists were awarded the American Potamkin Prize for their work on the amyloid precursor protein ...

*CLSTN1

... enhance the X11-like protein-mediated stabilization of amyloid beta-protein precursor metabolism". The Journal of Biological ... enhance the X11-like protein-mediated stabilization of amyloid beta-protein precursor metabolism". The Journal of Biological ... "Coordinated metabolism of Alcadein and amyloid beta-protein precursor regulates FE65-dependent gene transactivation". The ... "Coordinated metabolism of Alcadein and amyloid beta-protein precursor regulates FE65-dependent gene transactivation". The ...

*CTCF

"The zinc finger protein CTCF binds to the APBbeta domain of the amyloid beta-protein precursor promoter. Evidence for a role in ... This protein was found to be binding to three regularly spaced repeats of the core sequence CCCTC and thus was named CCCTC ... CTCF has also been shown to interact with Y box binding protein 1. CTCF also co-localizes with cohesin, which stabilizes the ... Cuddapah S, Jothi R, Schones DE, Roh TY, Cui K, Zhao K (2009). "Global analysis of the insulator binding protein CTCF in ...

*Calsyntenin

... enhance the X11-like protein-mediated stabilization of amyloid beta-protein precursor metabolism". J. Biol. Chem. 278 (49): ... Calsyntenins interact with numerous proteins such as with kinesin-1 and the APP-linker protein X11L/Mint2, and were shown to ... Rindler MJ, Xu CF, Gumper I, Cen C, Sonderegger P, Neubert TA (April 2008). "Calsyntenins are secretory granule proteins in ... Calsyntenins (Csts, CLSTN) also known as alcadeins are type I transmembrane proteins that belong to the cadherin superfamily. ...

*APLP1

Li Q, Südhof TC (2004). "Cleavage of amyloid-beta precursor protein and amyloid-beta precursor-like protein by BACE 1". J. Biol ... 1998). "Immunohistochemical and in situ analysis of amyloid precursor-like protein-1 and amyloid precursor-like protein-2 ... APLP1 amyloid beta (A4) precursor-like protein 1". Wasco W, Brook JD, Tanzi RE (January 1993). "The amyloid precursor-like ... 2003). "Processing of beta-amyloid precursor-like protein-1 and -2 by gamma-secretase regulates transcription". J. Biol. Chem. ...

*PSEN1

... from amyloid precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease. ... Selkoe DJ (1994). "Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease". Annu. Rev. ... APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein ... Pitsi D, Octave JN (June 2004). "Presenilin 1 stabilizes the C-terminal fragment of the amyloid precursor protein independently ...

*Glyceraldehyde 3-phosphate dehydrogenase

... skeletal muscle-specific Ca2+/calmodulin-dependent protein kinase; Akt; Beta-amyloid precursor protein (betaAPP); Huntingtin. ... For example, GAPDH interactions with beta-amyloid precursor protein (betaAPP) could interfere with its function regarding the ... GAPDH participates in a number of biological functions through its protein-protein interactions with: tubulin to facilitate ... where it ubiquitinates and degrades nuclear proteins during nitrosative stress conditions; GAPDH's competitor of Siah protein ...

*ANKS1B

"Amyloid-beta protein precursor (AbetaPP) intracellular domain-associated protein-1 proteins bind to AbetaPP and modulate its ... 2004). "The intracellular localization of amyloid beta protein precursor (AbetaPP) intracellular domain associated protein-1 ( ... Liu F, Su Y, Li B, Ni B (2003). "Regulation of amyloid precursor protein expression and secretion via activation of ERK1/2 by ... Ankyrin repeat and sterile alpha motif domain-containing protein 1B is a protein that in humans is encoded by the ANKS1B gene. ...

*Down syndrome research

APP is an Amyloid beta A4 precursor protein. It is suspected to have a major role in cognitive difficulties. Another gene, ETS2 ... Online Mendelian Inheritance in Man (OMIM) AMYLOID BETA A4 PRECURSOR PROTEIN; APP -104760, gene located at 21q21. Retrieved on ... Down syndrome individuals to develop Alzheimer's pathology is the gene that encodes the precursor of the amyloid protein. ... Neurofibrillary tangles and amyloid plaques are commonly found in both Down syndrome and Alzheimer's individuals. Layer II of ...

*Tm2 domain containing 1

Kirfel G, Borm B, Rigort A, Herzog V (2002). "The secretory beta-amyloid precursor protein is a motogen for human epidermal ... This protein may be a target of neurotoxic beta-amyloid peptide, and may mediate cellular vulnerability to beta-amyloid peptide ... The protein encoded by this gene is a beta-amyloid peptide-binding protein. It contains a structural module related to that of ... "Beta-amyloid peptide binding protein does not couple to G protein in a heterologous Xenopus expression system". J. Neurosci. ...

*APPBP1

The protein encoded by this gene binds to the beta-amyloid precursor protein. Beta-amyloid precursor protein is a cell surface ... APPBP1 (Amyloid Precursor Protein-Binding Protein 1) binds to the Amyloid Precursor Protein (APP) carboxy terminal domain. ... APPBP1 amyloid beta precursor protein binding protein 1". Chen Y, McPhie DL, Hirschberg J, Neve RL (March 2000). "The amyloid ... APPBP1 was first cloned and identified by its interaction with the C-terminus of beta-amyloid protein precursor (precursor to ...

*KIAA0825

The other is the Amyloid-beta precursor protein. This protein is an integral membrane protein found most commonly in the ... September 2011). "Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, ... Several programs suggest that the secondary structure of the protein is mainly helices with only a few beta sheets. Analysis of ... The subcellular localization for the protein is predicted to be the nucleus and the cytoplasm. This suggests that the protein ...

*Reelin

"Reelin in plaques of beta-amyloid precursor protein and presenilin-1 double-transgenic mice". Neuroscience Letters. 316 (3): ... "Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein". The ... Reelin has been shown to interact with amyloid precursor protein, and, according to one in-vitro study, is able to counteract ... "Interaction of reelin with amyloid precursor protein promotes neurite outgrowth". The Journal of Neuroscience. 29 (23): 7459-73 ...

*Estrogen and neurodegenerative diseases

JAFFE, AB; et.al (1994). "ESTROGEN REGULATES METABOLISM OF ALZHEIMER AMYLOID-BETA PRECURSOR PROTEIN". Journal of Biological ... Amyloid precursor protein (APP) proteolysis is fundamental for production of Aβ peptides implicated in AD pathology. By using a ... Amyloid plaques formed by amyloid-β (Aβ) deposition and neurofibrillary tangles formed by tau protein phosphorylation are ... The role of estrogens is mostly mediated by two nuclear receptors (ER alpha and ER beta) and a membrane-associated G-protein ( ...

*CTNNBIP1

Chen Y, Bodles AM (2007). "Amyloid precursor protein modulates beta-catenin degradation". Journal of Neuroinflammation. 4: 29. ... Beta-catenin-interacting protein 1 is a protein that is encoded in humans by the CTNNBIP1 gene. The protein encoded by this ... Sharma M, Henderson BR (2007). "IQ-domain GTPase-activating protein 1 regulates beta-catenin at membrane ruffles and its role ... 2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi: ...

*UBB+1

"Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients". Science. 279 (5348): ... Dennissen FJ, Kholod N, Steinbusch HW, Van Leeuwen FW (2010). "Misframed proteins and neurodegeneration: a novel view on ...

*SHC3

2002). "Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc". J. Biol ... SHC-transforming protein 3 is a protein that in humans is encoded by the SHC3 gene. SHC3 has been shown to interact with RICS ... Menegon A; Leoni C; Benfenati F; Valtorta F (1997). "Tat protein from HIV-1 activates MAP kinase in granular neurons and glial ... 1996). "A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding domains is related to Shc and is ...

*APBB1IP

Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP), also known as APBB1-interacting ... amyloid beta (A4) precursor protein-binding". Inagaki T, Suzuki S, Miyamoto T, Takeda T, Yamashita K, Komatsu A, Yamauchi K, ... 1997). "The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila ... protein 1 or Rap1-GTP-interacting adapter molecule (RIAM) is a protein that in humans is encoded by the APBB1IP gene. GRCh38: ...

*Carboxypeptidase B2

Matsumoto A, Itoh K, Matsumoto R (2000). "A novel carboxypeptidase B that processes native beta-amyloid precursor protein is ... Mosnier LO, Meijers JC, Bouma BN (2002). "The role of protein S in the activation of thrombin activatable fibrinolysis ... Mosnier LO, Elisen MG, Bouma BN, Meijers JC (2002). "Protein C inhibitor regulates the thrombin-thrombomodulin complex in the ... After thrombin activation, the mature protein downregulates fibrinolysis. Polymorphisms have been described for this gene and ...

*Cytochrome c oxidase

"Regional brain cytochrome oxidase activity in beta-amyloid precursor protein transgenic mice with the Swedish mutation". ... Aledo JC, Valverde H, Ruiz-Camacho M, Morilla L, López FD (2014). "Protein-Protein Interfaces from Cytochrome c Oxidase I ... The complex is a large integral membrane protein composed of several metal prosthetic sites and 14 protein subunits in mammals ... Soltys BJ, Gupta RS (1999). "Mitochondrial proteins at unexpected cellular locations: export of proteins from mitochondria from ...

*FBLN1

Ohsawa I, Takamura C, Kohsaka S (Mar 2001). "Fibulin-1 binds the amino-terminal head of beta-amyloid precursor protein and ... FBLN1 has been shown to interact with: NOV/CCN3, amyloid precursor protein, entactin, fibrinogen, and fibronectin. ... a novel protein that interacts with the fibronectin receptor beta subunit cytoplasmic domain". Cell. 58 (4): 623-9. doi:10.1016 ... Pan TC, Kluge M, Zhang RZ, Mayer U, Timpl R, Chu ML (Aug 1993). "Sequence of extracellular mouse protein BM-90/fibulin and its ...

*Michael Mullan

"Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene". Nature. 353: 844- ... Subsequently, he was a co-inventor on the original patents that covered three mutations in the amyloid precursor protein (APP) ... "Amyloid precursor protein in alzheimer's disease", published 1998-08-18 Goate A, Chartier-Harlin MC, Mullan M, Brown J, ... "Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease". Nature. 349: 704- ...

*LECT2

The secreted protein consists of 133`amino acids (mouse Alect2 consists of two varieties a typical 151 amino acid protein and ... It has been found repeatedly that the mere presence of LECT2 amyloid tissue deposits does not necessarily indicate the presence ... 2004). "Identification of the leukocyte cell-derived chemotaxin 2 as a direct target gene of beta-catenin in the liver". ... elevated in individuals not only with diagnosed metabolic syndrome but also with a characteristic of and possible precursor to ...

*Gamma secretase

"Familial Alzheimer's disease mutations inhibit gamma-secretase-mediated liberation of beta-amyloid precursor protein carboxy- ... The most well-known substrate of gamma secretase is amyloid precursor protein, a large integral membrane protein that, when ... complex with the γ-secretase activating protein facilitates the gamma cleavage of amyloid precursor protein into β-amyloid. The ... Zhang, H; Ma, Q; Zhang, YW; Xu, H (January 2012). "Proteolytic processing of Alzheimer's β-amyloid precursor protein". Journal ...
Amyloid beta-protein (A beta) is a proteolytic fragment of the amyloid beta-protein precursor (beta PP). Progressive cerebral deposition of A beta is an early and invariant feature of Alzheimers disease. The cellular trafficking of beta PP is of particular interest because understanding the production of A beta requires a comprehensive elucidation of the metabolic pathways of this protein. In addition, beta PP is a type I integral membrane glycoprotein that belongs to a class of molecules with both full length and secreted products. Recent evidence suggests that beta PP can be processed in an endosomal/lysosomal pathway. In the latter organelles, a number of beta PP carboxy-terminal derivatives are found, but the precise pathway and kinetics of beta PP trafficking from the cell surface remain unclear. To address these questions, we visualized directly the beta PP internalization pathway by following the localization and distribution of beta PP monoclonal antibodies added to intact beta ...
AICD, the C-terminal tail generated from the proteolytic cleavage of the Amyloid Precursor Protein (APP), has been generating interest for its transcriptional modulatory roles. AICD has been hypothesized to have such a function as it is generated by a gamma-secretase-mediated regulated intramembrane proteolysis step, analogous to the generation of Notch intracellular domain (NICD), a well-known transcriptional regulator, from Notch. The AICD/Fe65/Tip60 ternary complex has been proposed as the working transcriptional regulatory complex and some of its target genes have been reported. However, our knowledge of the functions of AICD is still limited due to difficulties in detecting and manipulating the rapidly degraded peptide. Looking at AICD transcription modulation targets from a genome-wide perspective will aid our understanding of the role of AICD tremendously. To this end, AICD chromatin binding sites were investigated from a genome-wide perspective by performing Chromatin Immunoprecipitation ...
The amyloid precursor protein gene (APP) and its derivative peptides have important functions in the central nervous system. APP and Aβ fulfil criteria as neuractive peptides: presence, release and identity of action. Aβ is a peptide of 1 - 43 amino acids in length, derived from APP and the major component of the core of neuritic plaques found in Alzheimers disease. Analysis of the cDNA of Aβ revealed its origins from the larger precursor protein. There are at least four types of mRNA generated by alternative splicing of exons 7 and 8. Exon 7 encodes a 57 amino acid sequence found in the extracellular domain with major homology to the Kunitz-type of serine protease inhibitors. APP is cleaved by three secretases known as α, β, and γ secretase which act on APP at different sites producing various fragments of differing amino acid length. The γ secretase is a macromolecular enzyme complex composed of presenilin 1, 2 and other molecular constitutents essential for its function.
The 4-kilodalton amyloid beta protein (A beta), which forms fibrillar deposits in Alzheimers disease (AD), is derived from a large protein referred to as the amyloid beta protein precursor (beta APP). Human neuroblastoma (M17) cells transfected with constructs expressing wild-type beta APP or a mutant, beta APP delta NL, recently linked to familial AD were compared. After continuous metabolic labeling for 8 hours, cells expressing beta APP delta NL had five times more of an A beta-bearing, carboxyl terminal, beta APP derivative than cells expressing wild-type beta APP and they released six times more A beta into the medium. Thus this mutant beta APP may cause AD because its processing is altered in a way that releases increased amounts of A beta. ...
9150PRTHomo sapiens 1Val Met Leu Lys Lys Lys Gln Tyr Thr Ser Ile His His Gly Val Val1 5 10 15Glu Val Asp Ala Ala Val Thr Pro Glu Glu Arg His Leu Ser Lys Met 20 25 30Gln Gln Asn Gly Tyr Glu Asn Pro Thr Tyr Lys Phe Phe Glu Gln Met 35 40 45Gln Asn 502134PRTHomo sapiens 2Ala Pro Lys Asn Glu Leu Val Gln Lys Phe Gln Val Tyr Tyr Leu Gly1 5 10 15Asn Val Pro Val Ala Lys Pro Val Gly Val Asp Val Ile Asn Gly Ala 20 25 30Leu Glu Ser Val Leu Ser Ser Ser Ser Arg Glu Gln Trp Thr Pro Ser 35 40 45His Val Ser Val Ala Pro Ala Thr Leu Thr Ile Leu His Gln Gln Thr 50 55 60Glu Ala Val Leu Gly Glu Cys Arg Val Arg Phe Leu Ser Phe Leu Ala65 70 75 80Val Gly Arg Asp Val His Thr Phe Ala Phe Ile Met Ala Ala Gly Pro 85 90 95Ala Ser Phe Cys Cys His Met Phe Trp Cys Glu Pro Asn Ala Ala Ser 100 105 110Leu Ser Glu Ala Val Gln Ala Ala Cys Met Leu Arg Tyr Gln Lys Cys 115 120 125Leu Asp Ala Arg Ser Gln 130325DNAArtificialPrimer APP_C50_F 3gtaccatatg gtgatgctga agaag 25432DNAArtificialPrimer APP_C50_R 4gtacaagctt ctagttctgc atctgctcaa ...
Alzheimer disease (AD) is a progressive neurodegenerative disorder pathologically characterized by deposition of ß-amyloid (Aß) peptides as plaques in the brain. Central to this AD pathology is mismetabolism of the amyloid precursor protein (APP). Recent studies suggest that flavonoids, a class of secondary plant metabolites, may be useful for the prevention and treatment of a variety of neurodegenerative diseases. The studies detailed herein, investigate the ability of two such classes of flavonoids, green tea derived catechins and 5,7-dihydroxyflavones, to modulate APP metabolism in Swedish mutant APP (APP[subscript]sw) models of AD. Studies showed that green tea derived (-)-epigallocatechin-3-gallate (EGCG) effectively reduced Aß generation and resultant amyloidosis both in vitro and in vivo. In concert with these findings, EGCG markedly promoted non-amyloidogenic APP proteolysis via activation of the putative a-secretase, a-disintegrin-and-metalloprotease-10 (ADAM10). Furthermore, luteolin and
Handling of Mice. The Tg2576 mice were developed by Karen Hsaio (Hsiao et al., 1996) and licensed from the Mayo Foundation for Medical Education and Research (Rochester, MN). Male Tg2576 transgenic mice were bred to normal C57BL6/SJL females at the Bristol-Myers Squibb facility in Wallingford, CT. Mice were housed with a 6:00 AM to 6:00 PM light/dark cycle and allowed free access to food and water. Both male and female mice were used in these studies, and although no differences in Aβ were observed between them, only one sex was used in a single study. Young Tg2576 mice were used between 3 and 6 months of age, whereas aged animals were used at 14 to 17 months. BMS-299897 was synthesized by the Medicinal Chemistry groups of SIBIA Neurosciences, Inc. (now Merck Research Laboratories, San Diego, CA) and Bristol-Myers Squibb. Animals were dosed by oral gavage in a volume of 6 ml/kg in polyethylene glycol, average molecular weight of 400, or a vehicle consisting of 10% propylene glycol, 7.5% ...
Amyloid beta precursor protein兔单克隆抗体可与小鼠, 大鼠, 人样本反应并经WB, IP, IHC,ICC, Flow Cyt实验严格验证,被21篇文献引用并得到5个独立的用户反馈。
Alzheimers disease is associated with a dramatic decline in cognitive performance including hippocampal-dependent memory. We have investigated one feature of hippocampal activity related to memory, the γ (30-80 Hz)-frequency rhythm. Hippocampal slices from mice overexpressing the human amyloid precursor protein (APP)SWE mutation (TAS10) were compared at 8 and 16 months of age with wild-type littermates. In slices obtained from TAS10 mice aged 8 months the γ-frequency activity evoked with bath application of 200 nm kainate was significantly (P , 0.05; n = 8 slices, five animals) impaired (area power, 5956 ± 2487 µV2) compared to slices from wild-type animals (area power, 18 256 ± 7880 µV2). At 16 months of age there was no longer a significant difference (P , 0.05; n = 11 slices from five animals) between slices from TAS10 and wild-type control mice as the wild-type mice now exhibited a marked age-dependent reduction in γ-frequency activity (TAS10 area power, 5751 ± 1573 µV2; wild-type ...
In mammals, many of the proteins taking part in the complex network of interactions centred at the cytosolic domain of APP belong to gene families. This is in fact the case for APP-like genes, as well as for Fe65- and X11-like members. APP-like gene family members have been analysed in depth, in mammals, by reverse genetics. However, their redundancy prevented the generation of clear phenotypes from murine knock-outs of the single APP, APLP1 or APLP2 genes ( Zheng et al., 1995; von Koch et al., 1997; Heber et al., 2000), whereas mice with combined knock-outs displayed severe phenotypes, dying early and post-natally. Taken together, the functions of these genes have been proposed as essential and partially redundant in mammals ( Heber et al., 2000). A similar phenotype, although not strictly predictable, might occur if reverse genetic approaches were used with the mammalian Fe65 gene family members. This was one of the reasons that prompted us to investigate potential Fe65-like genes in the ...
Recombinant Human Amyloid Precursor Protein Protein fragment datasheet (ab124588). Abcam offers quality products including antibodies, assays and other…
Iijima K, Ando K, Takeda S, Satoh Y, Seki T, Itohara S, Greengard P, Kirino Y, Nairn AC, Suzuki T. Neuron-specific phosphorylation of Alzheimers beta-amyloid precursor protein by cyclin-dependent kinase 5 ...
Numerous transmembrane proteins, including the blood pressure regulating angiotensin converting enzyme (ACE) and the Alzheimers disease amyloid precursor protein (APP), are proteolytically shed from the plasma membrane by metalloproteases. We have used an antisense oligonucleotide (ASO) approach to delineate the role of ADAM10 and tumour necrosis factor-α converting enzyme (TACE; ADAM17) in the ectodomain shedding of ACE and APP from human SH-SY5Y cells. Although the ADAM10 ASO and TACE ASO significantly reduced (, 81%) their respective mRNA levels and reduced the α-secretase shedding of APP by 60% and 30%, respectively, neither ASO reduced the shedding of ACE. The mercurial compound 4-aminophenylmercuric acetate (APMA) stimulated the shedding of ACE but not of APP. The APMA-stimulated secretase cleaved ACE at the same Arg-Ser bond in the juxtamembrane stalk as the constitutive secretase but was more sensitive to inhibition by a hydroxamate-based compound. The APMA-activated shedding of ACE ...
Liu F.L., Liu T.Y., Kung F.L.. One of the pathological hallmarks of Alzheimers disease is the presence of insoluble extracellular amyloid plaques. These plaques are mainly constituted of amyloid beta peptide (A beta), a proteolytic product of amyloid precursor protein (APP). APP processing also generates the APP intracellular domain (AICD). We have previously demonstrated that AICD interacts with FKBP12, a peptidyl-prolyl cis-trans isomerase (PPIase) ubiquitous in nerve systems. This interaction was interfered by FK506, a clinically used immunosuppressant that has recently been reported to be neuroprotective. To elucidate the roles of FKBP12 in the pathogenesis of Alzheimers disease, the effect of FKBP12 overexpression on APP processing was evaluated. Our results revealed that APP processing was shifted towards the amyloidogenic pathway, accompanied by a change in the subcellular localization of APP, upon FKBP12 overexpression. This FKBP12-overexpression-induced effect was reverted by FK506. ...
How is L-beta A4 amyloid precursor protein abbreviated? L-APP stands for L-beta A4 amyloid precursor protein. L-APP is defined as L-beta A4 amyloid precursor protein rarely.
Abnormal production and accumulation of amyloid-β peptide (Aβ) plays a major role in the pathogenesis of Alzheimers disease (AD). β-secretase (BACE1) is responsible for the cleavage at the β-site in amyloid β protein precursor (AβPP/APP) to generate
There are conflicting data regarding alterations in beta-amyloid precursor protein (APP) mRNAs in Alzheimers disease (AD). This may be due partly to variables such as agonal state and choice of control group. We have used in situ hybridization histochemistry to study expression of APP mRNAs, with and without the domain encoding the Kunitz protease inhibitor, in a way that overcomes some of the limitations of the current data. Tissue from frontal cortex was collected at rapid autopsy from patients with AD or other cognitive impairments whose terminal phase was prospectively assessed. There were three main findings. Firstly, the amount of APP mRNAs correlated strongly with glutamate decarboxylase activity and was reduced in association with terminal pyrexia. These correlations suggest that agonal state affects APP mRNA and, therefore, that differences in premortem course may contribute to the varying changes in APP transcript abundance reported in AD. Secondly, a reduction of both forms of APP mRNA,
Amyloid beta precursor protein gene (ABPP) encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a…
Insoluble beta-amyloid deposits in Alzheimers disease (AD) brain are proteolytically derived from the membrane bound amyloid precursor protein (APP). The APP gene is differentially spliced to produce isoforms that can be classified into those containing a Kunitz-type serine protease inhibitor domain (K(+), APP(751), APP(770), APRP(365) and APRP(563)), and those without (K(-), APP(695) and APP(714)). Given the hypothesis that Abeta is a result of aberrant catabolism of APP, differential expression of mRNA isoforms containing protease inhibitors might play an active role in the pathology of AD. We took 513 cerebral cortex samples from 90 AD and 81 control brains and quantified the mRNA isoforms of APP with TaqMan real-time RT-PCR. After adjustment for age at death, brain pH and gender we found a change in the ratio of KPI(+) to KPI(-) mRNA isoforms of APP. Three separate probes, designed to recognise only KPI(+) mRNA species, gave increases of between 28% and 50% in AD brains relative to controls ...
Antimicrobial peptides are important effector molecules of the innate immune system. Here, we describe that peptides derived from the heparin-binding disulfide-constrained loop region of human beta-amyloid precursor protein are antimicrobial. The peptides investigated were linear and cyclic forms of NWCKRGRKQCKTHPH (NWC15) as well as the cyclic form comprising the C-terminal hydrophobic amino acid extension FVIPY (NWCKRGRKQCKTHPHFVIPY; NWC20c). Compared with the benchmark antimicrobial peptide LL-37, these peptides efficiently killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Staphylococcus aureus and Bacillus subtilis, and the fungi Candida albicans and Candida parapsilosis. Correspondingly, fluorescence and electron microscopy demonstrated that the peptides caused defects in bacterial membranes. Analogously, the peptides permeabilised negatively charged liposomes. Despite their bactericidal effect, the peptides displayed very limited hemolytic ...
The findings of Massaad and colleagues will advance our basic understanding of the neuroprotective role of mitochondrially targeted antioxidants in Alzheimer disease (AD) pathogenesis. Their findings suggest that mitochondrial superoxide dismutase 2 (SOD2) decreases hippocampal superoxide radicals, ameliorates learning/memory deficits, and decreases amyloid-β (Aβ) plaques in double transgenic mice that overexpress SOD2 and mutant human amyloid precursor protein. Interestingly, they also found a decreased ratio of Aβ1-42 to 1-40 in double transgenic mice. These findings further support the mitochondrial oxidative damage hypothesis of AD, and may have important implications for mitochondrially targeted antioxidant therapeutics in AD.. Increasing evidence suggests that mitochondrial abnormalities are involved in the development and progression of AD (reviewed in Reddy, 2009). Further, it has been proposed that mitochondrially generated free radicals and oxidative damage are involved in abnormal ...
We have shown that the expression of a number of protective genes and a protective pathway culminating in Bad phosphorylation are increased in mice that overexpress APPSw and have no neuronal loss. Increased levels of IGF-2 mRNA and protein correspond to increased activation of the IGF-1 receptor, activation of Akt and Erk1/2, and phosphorylation of Bad in APPSw mice. The increased expression of TTR and IGF-2 as well as increased phospho-Bad staining in hippocampal neurons was consistent in both preplaque (6 months) and postplaque (12 months) Tg2576 mice. Other conditions, such as the presence of a human tau gene, may be necessary for complete AD pathology. However, taken together, these data imply that the lack of neurodegeneration in APPSw mice is a result of the activation of known cell survival pathways associated with the overexpression of APPSw.. Transthyretin has been shown to bind Aβ and inhibit Aβ aggregation (Schwarzman et al., 1994). In human AD patients the concentration of TTR is ...
Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimers disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered ...
Alzheimers Disease (AD) is genetically linked to the processing of amyloid b protein precursor (AbPP). Aside from being the precursor of the Amyloid
Production of soluble amyloid peptide precursor (APP) and amyloid peptide (A beta) was measured in CHO cells transfected by the wild-type APP 695 cDNA sequence or by the same sequence carrying missense mutations associated with familial Alzheimers disease in Sweden. Deletion of the C-terminal domain of the protein corresponding to residues 654 to 695 of APP 695 not only inhibited very significantly the internalization of APP at 37 degrees C, but also led to the secretion of an uncleaved APP in the culture medium of CHO cells. This deletion did not affect A beta production from the Swedish APP but was able to inhibit the production of the wild-type APP. These results demonstrate that, in CHO cells, the internalization of the wild-type APP is needed for A beta production, while the production of the amyloid peptide from Swedish APP is independent of the internalization process. ...
Background: Amyloid- neurotoxicity depends on the specificity of the proteolytic cleavage of the amyloid precursor protein (APP) transmembrane domain. Results: The APP transmembrane -helix is straight in a biological membrane bilayer. Conclusion: The flexibility of APP is key for adapting to the lipid environment and modulating proteolytic processing by -secretase. Significance: The dynamic characterization of APP is expected to rationalize the design of -secretase modulators. The amyloid precursor protein (APP) is a widely expressed type I transmembrane (TM) glycoprotein present at the neuronal synapse. The proteolytic cleavage by -secretase of its C-terminal fragment produces amyloid- (A) peptides of different lengths, the deposition of which is an early indicator of Alzheimer disease. At present, there is no consensus on the conformation of the APP-TM domain at the biological membrane. Although structures have been determined by NMR in detergent micelles, their conformation is markedly ...
The amyloid precursor protein (APP) is a large membrane protein whose C terminus projects into the extracellular space. In Alzheimers disease (AD), the APP is proteolytically cleaved at the N-terminal of ABeta by Beta-secretase (BACE) to release a ~100 kD APPsbeta protein into the extracellular space. The remaining 12 kD fragment remains membrane bound where it can be cleaved at its C-terminus by ( -secretase (presenilins) to release the insoluble Abeta peptide into the extracellular space with the ~8 kD APP C-terminal fragment (CTFbeta) remaining membrane bound. The APP is the subject of intensive investigations to determine how this protein is broken down abnormally in AD brains to give rise to Abeta, which is present in senile plaques and vessels. ...
Halim A., Brinkmalm G., Ruetschi U., Westman-Brinkmalm A., Portelius E., Zetterberg H., Blennow K., Larson G., Nilsson J.. The proteolytic processing of human amyloid precursor protein (APP) into shorter aggregating amyloid β (Aβ)-peptides, e.g., Aβ1-42, is considered a critical step in the pathogenesis of Alzheimers disease (AD). Although APP is a well-known membrane glycoprotein carrying both N- and O-glycans, nothing is known about the occurrence of released APP/Aβ glycopeptides in cerebrospinal fluid (CSF). We used the 6E10 antibody and immunopurified Aβ peptides and glycopeptides from CSF samples and then liquid chromatography-tandem mass spectrometry for structural analysis using collision-induced dissociation and electron capture dissociation. In addition to 33 unglycosylated APP/Aβ peptides, we identified 37 APP/Aβ glycopeptides with sialylated core 1 like O-glycans attached to Thr(-39, -21, -20, and -13), in a series of APP/AβX-15 glycopeptides, where X was -63, -57, -52, and ...
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In this work we assessed the role of ApoER2 in APP trafficking and processing in cells that do not express LRP1, another receptor of the LDL-R family previously described as a modulator of APP processing [64]. Our findings show that ApoER2 decreased APP internalization rate and increased the amount of APP that partitions into lipid rafts, where Aβ is produced. Interestingly, the expression of ApoER2 also significantly increased γ-secretase activity in two different cell types compared to controls. As a net result of these changes, Aβ levels were significantly increased. The effects that ApoER2 has on APP trafficking and processing might be direct, as ApoER2 and APP co-immunoprecipitate and co-localize at the cell surface of neuronal cells and are also found within the same intracellular vesicles upon internalization. Our results show that ApoER2 increases Aβ production despite elevated cell surface APP levels, due to effects on APP association with lipid rafts and γ-secretase activity. This ...
These transgenic mice exhibit increasing expression of human amyloid beta precursor protein in the cortex, hippocampus, brain stem, and cerebellum with age. This mutant mouse strain may be useful in studies of Alzheimers disease.
Amyloid precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation, neural plasticity and iron export. APP is best known as the precursor molecule whose proteolysis generates beta amyloid (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimers disease patients. APP is an ancient and highly conserved protein. In humans, the gene for APP is located on chromosome 21 and contains 18 exons spanning 290 kilobases. Several alternative splicing isoforms of APP have been observed in humans, ranging in length from 639 to 770 amino acids, with certain isoforms preferentially expressed in neurons; changes in the neuronal ratio of these isoforms have been associated with Alzheimers disease. Homologous proteins have been ...
In conclusion, we provide evidence for the first time that polymorphisms located in the 3UTR of hAPP may affect its expression, at least in the experimental conditions tested here. Indeed, we show that two AD-specific 3UTR variants previously identified by Bettens and colleagues [20] affect the modulating activity of miR-147 and miR-20a on the expression of APP. SNP T171C decreases the ability of miR-147 to down-regulate APP, theoretically leading to increased APP and Aβ production. On the other hand, SNP A454G increases the effect of miR-20a, suggesting that APP expression is reduced in these patients. Although these data seem to contradict with the main hypothesis that increased APP levels lead to AD, some reports indicate that decreasing the APP levels might have deleterious consequences in the brain [24, 25]. Another possibility is that miR-20a levels (or function) vary depending on brain region or disease state, therefore only locally affecting APP. In line with this hypothesis, our ...
Complete information for APBB1 gene (Protein Coding), Amyloid Beta Precursor Protein Binding Family B Member 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
1AQC: Sequence-specific recognition of the internalization motif of the Alzheimers amyloid precursor protein by the X11 PTB domain.
... (APP) is a type-I transmembrane protein enriched in neuronal tissues that undergoes sequential proteolytic processing through two distinct pathways. One pathway generate non-pathogenic molecules while the other generates Amyloid β (Aβ), which accumulates resulting in neurotoxicity and is associated with Alzheimers disease. BioLegend provides an extensive collection of antibodies and reagents for the study of APP and Aβ. BioLegend develops and manufactures world-class, cutting-edge immunological reagents for biomedical research, offered at an outstanding value.
This study demonstrates that pre-plaque TgCRND8 mice exhibit early behavioral alterations only in a subset of hippocampal-dependent tasks associated with drastic deficits in hippocampal inhibitory networks and altered γ oscillations. Strikingly, we showed that different APP metabolites were likely responsible for specific memory deficits in two different tasks. Overall, our study supports the current hypothesis that Aβ is unable to account for all aspects of cognitive impairments in AD, highlighting the complexity of the amyloid pathology.. As the field inches toward early detection of AD to provide precocious treatment (34), it is critical to assess the respective role of each APP fragment in the earliest stage of the disease. Hence, we focused our work on young adult TgCRND8 mice, a well-characterized mouse model of AD-like amyloid pathology (22). In this mouse model, robust expression of Aβ begins around 10 weeks of age, and amyloid deposits appear at 3 months (22). Therefore, we ...
Recent reports have suggested that elevated cholesterol levels may modulate processing of beta-amyloid precursor protein (APP) by increasing formation of the amyloid-beta (Aβ) peptide, a central event in the pathogenesis of Alzheimers disease (AD). Cholesterol accumulation in endosomes/lysosomes in Niemann-Pick Type C (NPC) disease is accompanied by a significant increase in Aβ levels and levels of the Cterminal APP fragment - C99. The goal of this work was to investigate the cholesterol accumulation-regulated subcellular redistribution of APP and/or presenilin 1 (PS1) in NPC disease. To test this we utilized NPC model cells (CHO NPC1-null) and parental CHOwt cells. Using subcellular fractionation we observed altered subcellular localization of APP and PS1 together with increased C99 levels in early/late endosomes in CHO NPC1-null vs. CHOwt cells. Our findings suggest that cholesterol may contribute to AD onset by altering trafficking of APP and PS1 within endocytic pathway leading to ...
To prove that this polypeptide indeed represents the γ‐secretase‐generated CTFγ, we treated HEK 293 cells stably transfected with swAPP with the previously described γ‐secretase inhibitor DAPT (Dovey et al., 2001). As shown in Figure 1B and C, concomitant with an increase of βAPP CTFβ and CTFα (Figure 1B, upper panel) a dose‐dependent inhibition of CTFγ generation was observed (middle panel). This was further confirmed by the immunoprecipitation of Aβ from the conditioned media of these cells, which consistent with previous results (Dovey et al., 2001) also revealed a dose‐dependent reduction of Aβ generation (Figure 1B, lower panel and C). Similar results were also obtained with N2a cells (data not shown). To further prove the PS dependence of this cleavage, we immunoprecipitated βAPP and its proteolytic fragments from cells expressing PS1 D385N. As shown previously (Steiner et al., 1999; Wolfe et al., 1999), PS1 D385N acts like a dominant‐negative mutation that inhibits ...
Identification of heparin-binding domains in the amyloid precursor protein of Alzheimers disease by deletion mutagenesis and peptide mapping
Amyloid-β-protein (Aβ), the key component of senile plaques in Alzheimers disease (AD) brain, is produced from amyloid precursor protein (APP) by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB) domains, including Dab (gene: DAB) and Numb (gene: NUMB), can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells) or APP-C99 (H4-APP-C99 cells) increased levels of APP-C-terminal fragments (APP-CTFs) and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel
The etiology of Alzheimers disease (AD) is complex with oxidative stress being a possible contributory factor to pathogenesis and disease progression. TASTPM transgenic mice expressing familial AD-associated amyloid precursor protein (APPswe) and presenilin transgenes (PS1M146V) show increased brain amyloid beta (Abeta) levels and Abeta plaques from 3 months. We tested if enhancing oxidative stress through diet would accelerate Abeta-related pathology. TASTPM were fed a pro-oxidant diet for 3 months resulting in increased brain levels of protein carbonyls, increased Nrf2, and elevated concentrations of glutathione (GSH). The diet increased both amyloid precursor protein (APP) and Abeta in the cortex of TASTPM but did not alter Abeta plaque load, presenilin 1, or beta-secretase (BACE1) expression. TASTPM cortical neurons were cultured under similar pro-oxidant conditions resulting in increased levels of APP and Abeta likely as a result of enhanced beta/gamma secretase processing of APP. Thus, ...
Sontag, E. et al. (2007) Protein Phosphatase 2A Methyltransferase Links Homocysteine Metabolism with Tau and Amyloid Precursor Protein Regulation. J. Neurosci. 27(11):2751-2759.. Phosphorylated amyloid beta and tau peptides are associated with AD. Homocysteine may be linked to AD risk because it increases SAH levels, inhibiting methyltransferase-dependent reactions. Neuroblastoma cells incubated with SAH showed reduced methylation of protein phosphatase 2A (PP2A), which leads to reduced substrate specificity and accumulation of both phosphorylated tau and APP isoforms as well as an increase in beta secretase-cleaved APP fragments and amyloid beta peptides. SAH and SAM-treated Neuro-2a cells were lysed and used in Western blot analysis; blots were probed with anti-APP beta antibody.. Matsuda, S. et al. (2008) BRI2 Inhibits Amyloid β-Peptide Precursor Protein Processing by Interfering with the Docking of Secretases to the Substrate. J. Neurosci. 28(35):8668-8676.. Two familial Alzheimers disease ...
Sontag, E. et al. (2007) Protein Phosphatase 2A Methyltransferase Links Homocysteine Metabolism with Tau and Amyloid Precursor Protein Regulation. J. Neurosci. 27(11):2751-2759.. Phosphorylated amyloid beta and tau peptides are associated with AD. Homocysteine may be linked to AD risk because it increases SAH levels, inhibiting methyltransferase-dependent reactions. Neuroblastoma cells incubated with SAH showed reduced methylation of protein phosphatase 2A (PP2A), which leads to reduced substrate specificity and accumulation of both phosphorylated tau and APP isoforms as well as an increase in beta secretase-cleaved APP fragments and amyloid beta peptides. SAH and SAM-treated Neuro-2a cells were lysed and used in Western blot analysis; blots were probed with anti-APP beta antibody.. Matsuda, S. et al. (2008) BRI2 Inhibits Amyloid β-Peptide Precursor Protein Processing by Interfering with the Docking of Secretases to the Substrate. J. Neurosci. 28(35):8668-8676.. Two familial Alzheimers disease ...
Book plaque-like "AMY" lesions were recently described in the brains of individuals with Alzheimers disease (Advertisement). APP transgenic mice aged 8 to 20 weeks demonstrated Aβ IR but no Rabbit Polyclonal to PLD2. AMY IR. We conclude that AMY IR represents an amyloid-associated antigen that co-deposits generally in most however not all Aβ plaques in Advertisement and DS which accumulation from the AMY antigen comes after Aβ deposition in plaques. Alzheimers disease (Advertisement) can be characterized neuropathologically by the current presence of two principal mind lesions amyloid plaques and neurofibrillary tangles. The sooner of both lesions the amyloid plaque can be formed from the intensifying extracellular deposition in mind parenchyma of heterogeneous amyloid β-peptides (Aβ) proteolytically produced from the β-amyloid precursor proteins (βAPP). 1 As the βAPP gene can be encoded on chromosome 21 and it is overexpressed in trisomy 21 (Down symptoms (DS)) DS offers a temporal ...
Calcium plays a fundamental role for the biological activity of nerve cells and there is growing evidence that degeneration of nerve cells in Alzheimers disease is causally related to disturbations in Ca2+ homeostasis. Studies on inherited forms of Alzheimers disease (familial Alzheimers disease) have indicated a role of presenilins and APP (Amyloid Precursor Protein) in this process. Metabolic processing of APP, which involves presenilins, can result in the release of a small fragment which is called AICD (APP intracellular domain). There is emerging evidence that AICD plays a pivotal role in Alzheimers disease. At least two metabolic products of APP, AICD and sAPPalpha have been implicated in the regulation of gene activity and the major aim of this project was to correlate both APP-dependent gene regulation and disruption of calcium homeostasis with the molecular mechanisms leading to neuronal cell death in AD. Our data obtained demonstrate that both APP and AICD can significantly ...
LC degeneration is a well known feature of AD (Forno, 1966) and correlates with its clinical and histopathological changes (Bondareff et al., 1987; Zarow et al., 2003). Loss of LC neurons occurs early in AD (German et al., 1992) and subsequently attenuates the allocation of NA to respective projection areas (Adolfsson et al., 1979; Mann et al., 1980). Using amyloid plaque-containing APP transgenic mice (APP23), we show that LC degeneration and the resulting NA depletion increase inflammation and amyloid plaque formation. Furthermore, NA depletion in combination with amyloid deposits leads to a decrease in neuron number and in neuronal function as determined by micro-PET and behavioral studies in vivo. Our results indicate that LC degeneration may contribute significantly to the pathogenesis of AD.. In addition to its function as a classical neurotransmitter, NA exerts potent anti-inflammatory effects in the brain (for review, see Feinstein et al., 2002). Consistent with this notion, we found ...
Purpose: Death of retinal ganglion cells (RGCs) is one of the key pathogenic features of glaucoma. The accumulation of amyloid beta (Aβ) may contribute to the RGC death. Olfactomedin 1 (Olfm1), also known as noelin and pancortin, is a secreted glycoprotein highly conserved in vertebrates. Olfm1 belongs to the family of olfactomedin domain-containing proteins, and is expressed both in the retina and brain. Available data suggest that Olfm1 may interact with amyloid precursor protein (APP), suppress its cleavage, and inhibit the subsequent production of Aβ. The mechanisms of APP cleavage inhibition by Olfm1 are unknown. Here, we investigated these mechanisms.. Methods: Primary RGS cultures were established using an immunopanning method from 1 to 5 day-old mice. Interactions between Olfm1 and putative Olfm1 binding proteins were investigated with an alkaline phosphatase fusion protein assay, as well as a co-immunoprecipitation assay using lysates of HEK293 cells transfected with corresponding ...
Alzheimers disease (AD) as one of the ongoing neurological disorders is initiated and progressed by multiple pathological pathways. Cargoes trafficking pathways, such as recycling, play a crucial role in the pathogenesis of AD. One of the major constituents of this trafficking system in neurons is retromer which acts in endosomal sorting machinery. Defective retromer disrupts recycling of cargoes from endosomes to Golgi and leads to its mis-trafficking which may subsequently leads to AD. Also, retromer-related cargo trafficking could trigger amyloidogenic pathway and beta-amyloid production. Wingless is another cargo in Wnt pathways and its trafficking is mediated by retromer. Retromer malfunction leads to lack of Wnt and subsequent AD-related pathogenesis. Also, retromer plays role in synaptic receptor trafficking in physiologic and pathologic conditions. This review is brief survey on the recent published literatures about pathogenesis of retromer-related trafficking in amyloid precursor protein
摘 要:淀粉样前体蛋白(amyloid precursor protein,APP) 是一类与阿尔茨海默氏病(Alzheimer{$39}s disease,AD)的发生、发展密切相关的I型跨膜蛋白,具有膜受体样结构,但迄今人们对APP真正的生理功能仍知之甚少。近年来研究发现,APP分子间可以进行二聚化,并且反式的二聚化作用有促进细胞黏附的功能。而APP的降解产物b-淀粉样蛋白 (b-amyloid protein, Ab) 反过来又可以加速APP的聚集,经过一系列反应,最终引发细胞凋亡。本文综述这一领域的研究进展,特别是APP的相互作用,以及这些相互作用对细胞状态和行为的影响 ...
This protein protein interaction antibody pair set comes with two antibodies to detect the protein-protein interaction, one against the NEFL protein, and the other against the APP protein for use in in situ Proximity Ligation Assay. See Publication Reference below. (DI0062) - Products - Abnova
APP is a transmembrane glycoprotein widely present in various tissues, containing a longer fragment of the extracellular amino-terminal (N-terminal) and short segments of the intracellular carboxy-terminal (C-terminal), and its encoding gene is located on the first human 21 chromosome 21q21.2, the transcription, translation and processing mainly expressed in the formation of three kinds with different length of the peptide chain isoforms, APP695, APP751 and APP770. Compared with the other two isoforms, APP695 lacks the Kunitz protease inhibitor (KPI) region outside the cell. Neurons expressing APP695 subtypes in the cerebral cortex of APP695, APP751 and APP770 mRNA ratio of 20:10:1. The function of APP may be: (1) G protein-coupled receptor-like role to participate in transmembrane signal transduction process. (2) to promote cell adhesion, cell shape remodeling and neural development. (3) to promote the occurrence of synaptic structure, and enhance synaptic plasticity and synaptic transmission. ...
APP is a transmembrane glycoprotein widely present in various tissues, containing a longer fragment of the extracellular amino-terminal (N-terminal) and short segments of the intracellular carboxy-terminal (C-terminal), and its encoding gene is located on the first human 21 chromosome 21q21.2, the transcription, translation and processing mainly expressed in the formation of three kinds with different length of the peptide chain isoforms, APP695, APP751 and APP770. Compared with the other two isoforms, APP695 lacks the Kunitz protease inhibitor (KPI) region outside the cell. Neurons expressing APP695 subtypes in the cerebral cortex of APP695, APP751 and APP770 mRNA ratio of 20:10:1. The function of APP may be: (1) G protein-coupled receptor-like role to participate in transmembrane signal transduction process. (2) to promote cell adhesion, cell shape remodeling and neural development. (3) to promote the occurrence of synaptic structure, and enhance synaptic plasticity and synaptic transmission. ...
Evidence-Based Complementary and Alternative Medicine (eCAM) is an international peer-reviewed, Open Access journal that seeks to understand the sources and to encourage rigorous research in this new, yet ancient world of complementary and alternative medicine.
BioAssay record AID 144358 submitted by ChEMBL: Compound was tested for the inhibition of 1-40 beta-Amyloid Production in N9 cell line expressing beta-APP (wascreated by transfecting the human cDNA encoding beta-APP 695) by using immunoprecipitation assay.
Data that have accumulated for well over a decade have implicated the β-amyloid (Aβ) peptide as a central player in the pathogenesis of Alzheimers disease (AD). Amyloid plaques, composed primarily of Aβ progressively form in the brains of AD patients, and mutations in three genes (amyloid precursor protein [APP] and presenilin 1 and 2 [PS1 and PS2]) cause early-onset familial AD (FAD) by directly increasing production of the toxic, plaque-promoting Aβ42 peptide. Given the strong association between Aβ and AD, it is likely that therapeutic strategies to lower the levels of Aβ in the brain should prove beneficial for the treatment of AD. One such strategy could involve inhibiting the enzymes that generate Aβ. Aβ is a product of catabolism of the large type-I membrane protein APP. Two proteases, called β- and γ-secretase, endoproteolyze APP to liberate the Aβ peptide. Recently, the molecules responsible for these proteolytic activities have been identified. Several lines of evidence ...
We report that F-spondin, a secreted protein that is thought to function in brain development and neuronal repair (26-32), can bind to the conserved CAPPD, and we show that F-spondin binding can control cleavage of APP by BACE 1, which cleaves APP C-terminal to the CAPPD. The evidence for these conclusions is based on four principal findings: (i) F-spondin is efficiently captured by Ig- and GST-fusion proteins of APP (Fig. 1); (ii) APP is affinity-purified on immobilized Ig-F spondin fusion proteins (Fig. 2); (iii) coexpression of Ig-F spondin with APP and BACE 1 inhibits cleavage of APP in a dose-dependent manner (Figs. 4 and 5); and (iv) cotransfection of Ig-F spondin impairs APP-dependent transactivation of transcription mediated by Gal4-Tip60 (Fig. 6). As controls, we show that APP does not bind to other proteins, including an Ig-fusion protein of Mindin that contains a subset of domains present in F-spondin (Fig. 3). Our data only addressed BACE 1-dependent APP cleavage directly, but it ...
These transgenic mice express the human amyloid precursor protein bearing the Swedish (K670N/M671L) mutation and develop amyloid deposits in brain tissue by 18-20 months of age. These mice provide a useful model for studying the underlying mechanism of amyloid deposition, a process implicated in Alzheimers disease (AD).
In the present study, we examined the consequences of FE65 and FE65L1 deficiencies on mammalian brain development in mice. Until now, our understanding of the function of the FE65 family in vivo was limited to its role at the C. elegans neuromuscular junction (Zambrano et al, 2002; Bimonte et al, 2004). We report that the FE65 and FE65L1 proteins are required for integrity of the pial basement membrane, neuronal positioning and the establishment of normal axonal projections during cortical development. Furthermore, the phenotypes of the FE65 and FE65L1 double knockout share remarkable similarities with that reported for mutant mice lacking FE65‐binding partners, the three members of the APP gene family, that is APP, APLP1 and APLP2 (Herms et al, 2004), and the Ena/Vasp protein family (Lanier et al, 1999).. Molecules implicated in neuronal migration such as those necessary for locomotion, nucleokinesis and adhesion of migrating neurons along radial glia contribute to cortical development (Marin ...
An important biochemical hallmark of AD is the accumulation of proteinaceous deposits known as amyloid plaques in brain tissue. The primary constituents of amyloid plaques are aggregated amyloid-β (Aβ) peptides, which are neurotoxic. These 40- to 42-amino acid peptides are derived from the amyloid precursor protein (APP), a single pass transmembrane protein that is widely expressed in many tissues. There are eight isoforms of APP, ranging from 365 to 770 amino acids in length. The exact function of APP is unknown, though evidence suggests that it plays a role in the formation and repair of neural synapses, where expression levels of the 695 amino acid isoform are particularly high. APP undergoes extensive postranslational modifications, including proteolytic cleavage by a number of enzymes. There are two primary pathways for APP proteolysis. The first, nonamyloidogenic pathway is initiated by the enzyme α-secretase, which produces a transmembrane C83 fragment and a soluble APPsα fragment. ...
Accumulation of beta-amyloid as plaques between neurons in the brain is a primary pathological feature of Alzheimers disease. Amyloid is a general term for protein fragments produced normally by the body. Beta-amyloid is a protein fragment snipped from an amyloid precursor protein (APP). In a healthy brain these protein fragments are broken down and eliminated, but in Alzheimers disease the fragments accumulate to form hard, insoluble plaques. These plaques have been correlated with neurotoxicity and the cognitive decline associated with the disease ...
While predisposition to AD has been linked to mutations of several genes, including those of presenilins and apolipoprotein E, mainly two protein components are present in the two types of AD aggregates (reviewed in Hardy and Selkoe, 2002). Plaques are generated by deposition of the amyloid peptides (Aβ), which are degradation products of the amyloid precursor protein (APP). APP is a transmembrane cell surface glycoprotein, expressed in five isoforms, with APP(695) being the dominant isoform in brain. APP can be cleaved by three different proteases, called α, β and γ secretases. When APP is concomitantly hydrolysed by β‐secretase at the N‐terminus of Aβ and by the γ‐secretase within the membrane (Lichtenthaler et al., 2002), the two main products, Aβ(1-40) and Aβ(1-42), migrate outside the cell and give rise to fibrils. When APP is cut by α‐secretase, the resulting soluble peptides are generally considered non‐toxic, although a recent report shows that the p3 peptide derived ...
Authors: Sparks, D. Larry , Lochhead, Jeff , Horstman, Donna , Wagoner, Tom , Martin, Tim Article Type: Research Article Abstract: Increased circulating cholesterol is known to promote risk of coronary artery disease. It is now emerging that cholesterol promotes production and accumulation of amyloid β (Aβ) deposited in the hallmark pathologic lesion of Alzheimers disease (AD), the senile plaque, perhaps by shifting away from normal metabolism of amyloid β protein precursor (AβPP) to β. Previous studies employing the cholesterol-fed rabbit model of AD demonstrated that induction of AD-like Aβaccumulation in brain could be reversed by co-administration of cholesterol lowering drugs or removing cholesterol, prompted initiation of an AD Cholesterol-Lowering (Statin) Treatment Trial. We now present data that identify a previously …unrecognized role for dietary water quality on the severity of neuropathology induced by elevated cholesterol. Neuronal accumulation of Aβ induced by increased ...
Phosphorylation of T668 was shown to induce cis‐isomerization of proline P669, resulting in a destabilization of the helix cap T668PEE (Ramelot & Nicholson, 2001). The importance of isomerization is emphasized by the interaction of the phosphorylated APP C terminus with prolyl isomerase 1 (Pin1), which accelerates isomerization 1,000‐fold and directly influences APP processing and Aβ production (Pastorino et al, 2006). To test the importance of residue T668 for Fe65‐PTB2 binding and APP C terminus conformation, we solved the AICD/Fe65‐PTB2 structures of the T668A and T668E point mutants, which lack a polar side chain or have been thought to mimic a phospho‐threonine, respectively (supplementary Table S1 online). The two mutations in the full‐length APP have been found previously to impair Fe65 binding both in vitro and in vivo (Ando et al, 2001). In both structures, the helical cap and helix αN are destabilized, as judged from a relative increase of the temperature factors, ...
Discovering new targets for Alzheimers disease is of key importance in developing better treatments. Learn about APP-C31, a new potential target!
If the product specification or packaging standard is revised, the images and the actual product specification might be different ...
Principal Investigator:TAKAHATA Naohiko, Project Period (FY):1995 - 1996, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Psychiatric science
Giving patients easy access to own medical records is a key goal of health reformers. The Obama administration has pressed doctors, hospitals, government agencies and businesses to make patient health
Yes, if you happen to own more than one Android device, youre welcome to install the app on multiple devices. Each device syncs through your Remember The Mi...
Effects of E682K mutation on APP processing in cultured neuronsA. Primary cultured neurons were transduced with SFV expressing WT or mutant APP. Cell lysates we
Apbb1 is an adapter protein that forms a transcriptiolly active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular…
购买我们的重组人Amyloid Precursor蛋白。Ab124588为蛋白片段,在大肠杆菌中生产并经过SDS-PAGE, Mass Spectrometry实验验证。Abcam提供免费的实验方案,操作技巧及专业的支持。
Portelius, E; Westman-Brinkmalm, A; Zetterberg, H; Blennow, K. Determination of ß-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry. Journal of proteome research. 5, 1010-1016, 2006. • Portelius, E; Price, E; Brinkmalm, G; Stiteler, M; Olsson, M; Persson, R; Westman-Brinkmalm, A; Zetterberg, H; Simon, AJ; Blennow, K. A novel pathway for amyloid precursor protein processing. Neurobiol Aging, doi:10.1016/j.neurobiolaging.2009.06.002, 2009. • Portelius, E; Dean, RA; Gustavsson, MK; Andreasson, U; Zetterberg, H; Siemers, E; Blennow K. Amyloid beta isoforms in CSF reflect gamma- secretase inhibition in Alzheimers disease. Alzheimer´s disease and therapy. 2(2) 7, 2010. ...
FocusAssist, a feature of the Mindflash app, monitors the attention of someone watching a training course and pauses the app when the person looks away.
BRI3 binding protein. Plays a role in tumorigenesis. BRI3 is a member of the BRI gene family that includes the familial British and Danish dementia gene BRI2. BRI3 interacts with the Amyloid Precursor Protein, APP, and serves as an endogenous negative regulator of Abeta production (Matsuda et al. 2009 ...
A recent study found that the free Android app, Tät, helped many women reduce the severity of their symptoms in three months time.
Genetic Inhibition of Phosphorylation of the Translation Initiation Factor eIF2alpha Does Not Block Abeta-Dependent Elevation of BACE1 and APP Levels or Reduce Amyloid Pathology in a Mouse Model of Alzheimers Disease ...
Read reviews, compare customer ratings, see screenshots, and learn more about The Waterlow Score App. Download The Waterlow Score App and enjoy it on your iPhone, iPad, and iPod touch.
Read reviews, compare customer ratings, see screenshots, and learn more about Pregnancy Tracker & Baby App. Download Pregnancy Tracker & Baby App and enjoy it on your iPhone, iPad, and iPod touch.
By request heres Pregtool. Its an app that calculates a pregnant womans due date based on either the date of her last period or the gestation age of the fetus as determined by an Ultrasound examination. Intended for medical professionals, this app can also be used by expectant parents. The fields in the app are labeled rather cryptically but the app is easy to use:. ...
玩免費【Rapid Notes Pro】iOS、Android、Windows跨平台APP在本站24hr提供note everything pro破解,note everything pro繁體全球最夯APP下載點隨便你挑選,note everything pro add on下載这是Pro版本的应用程序的
CIE 10 PREMIUM線上破解APP新玩法懶人包,詳細解說醫療APP手遊最新APP消息,不能錯過全世界Android App Store、iOS App Store、Windows App Store搶先資訊ICD 10 Indonesia-English app,idc 10熱門APP載點排行榜,idc 10 pinLa CIE10 es el acrónimo de la Clasificación internacional de enfermedades, décima versión correspondiente a la versión en español de la (en inglés) IC
The Super Debugger (superdb for short) is a dynamic, wireless debugger for iOS (and theoretically, Mac) apps. It works as two parts: a static library that runs built in to your app and a Mac app to send commands to the app, wirelessly. Your app starts up the debugger via this library, which broadcasts itself on your local network. The Mac app can discover these debug sessions via Bonjour and connect to them.

You can then send messages to your live objects as the app is running on the device (or Simulator). No need to set any break points. Any message you can send in code can also be sent this way. This allows you to rapidly test changes and see their results, without the need to recompile and deploy.

The debugger will even let you rapidly resend messages involving numeric values. When trying to tweak an interface measurement, for example, you can just click and drag on the value and see the changes reflected instantly on the device. | Complex Insight - Understanding our world
[button size=small text=MSDS & Datasheet link=/wp-content/uploads/media/BCDatasheets_C_10.26/FXXXX/F-8003-1.pdf]FITC Conjugated Aegopodium podagr
手機推薦健康實用APP《PDA Dentist》在本站分享如何使用APP、APP攻略詳情以及破解版APP供網友免費下載路徑新聞 app,東森新聞找好用健康 APP?免費APP快訊都在這裡推薦,蘋果動新聞Our free app will make it fun to brush your teeth! The app will play your favorite tunes, keep a brushing history, time your brushes, and give you poi
We screened 115 patients, enrolled 20 patients (17.4%), and completed follow-up interviews with 17 patients (85%). Reasons for nonenrollment included: failure to meet inclusion criteria (47/115, 40.9%), declined to participate (26/115, 22.6%), and other reasons (22/115, 19.1%). There was no difference in patient ratings between usability at first-use and after extended use, with SUS scores greater than the 95th percentile at both time points. Despite high usability ratings, 6/20 (30%) of patients never used the app at home after hospital discharge and 2/20 (10%) only used the app once. Interviews revealed three themes related to app use: (1) patient-related barriers could prevent use even though the app had high usability scores; (2) patients viewed the app as a second opinion, rather than a primary source of information; and (3) many patients viewed the app as an external burden.. CONCLUSIONS ...
This is what Charlie Manuel said about the possibility of finding a start for J.A. Happ: “We’ll consider doing anything we have to do…I don’t mean we’re going to put Happ in the rotation just yet.” Given the rotation’s atrocious numbers and Happ’s strong spring training and bullpen work, the young man seems like he could help out as a starter. But as you all know, that’s tricky. How do you get him in there? Moyer has a two-year contract and wouldn’t be an ideal reliever, Myers has re-committed to starting, Park earned himself another few turns…. I’m leaving for Philly in two minutes and won’t be covering the game tomorrow, but I’ll leave you with a question: What do you think the team should do about Happ? Don’t just say “start him;” come up with a plan for how, if that’s what you think should happen. - Andy Martino, Philadelphia Inquirer
For all women regardless of whether they have been diagnosed with breast cancer or not, this app helps patients keep track of their mammogram appointments. If newly diagnosed, this app can also help breast cancer patients prepare for important upcoming visits with physicians. The app helps patients create a list of questions for your doctor by providing patients with highly personalized suggestions. Then, during your visit, save typed notes to your questions or record audio of your conversation. Youll get the most out of every visit and make sure you never forget any of the important information from your doctors ...
You can subscribe to your iCalendar feed so that your calendar app can stay up-to-date with your Remember The Milk tasks. Calendar apps such as Apple Calenda...
Air Products Pipe Pigout app can calculate the nitrogen volume, flow rate and pressure suitable to push your pig and complete the purge or displacement of your pipeline.
Kosmo is your smart coach to drive you on the road to quitting. The Kosmo is a smart, connected vaporizer that when paired with your smartphone app can t
This page provides description of the page components that you create for your app are based on the /libs/mobileapps/components/angular/ng-page component (CRXDE Lite on a local server).
Visit Healthgrades for information on Dr. Jennifer Sapp, DO Find Phone & Address information, medical practice history, affiliated hospitals and more.
Survivalcraft by Igor Kalicinski: You are marooned on the shores of an infinite blocky world. Explore, mine resources, craft tools and weapons, hunt, make traps and grow plants. Build a shelter to survive nights and share your worlds ...
Lovely is a wearable sex toy for couples that learns what a given couple likes in bed and suggests simple tips through the Lovely App on how to have an even better sex next time. Using a Lovely enhances the quality and diversity in a couples sex life thanks to the unmatched wealth of knowledge and innovation put...
I tend to find myself in the terminal.app on my Mac more often than not, SSHing into servers, checking whois, host, and any number of other things. My most frequent incantation is searching the command history so I dont have to re-type a previous command, something like this:. ...
Amyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.
Objective: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood-brain barrier (BBB) impairment.. Methods: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25-12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (Aβ38, Aβ40, Aβ42, sAPPα, and sAPPβ), and BBB function (CSF:serum albumin ratio).. Results: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS ,1 year. Athletes with PCS ,1 year had higher RPQ scores and number of concussions than athletes with PCS ,1 ...
Metal binding to the amyloid beta-peptide is suggested to be involved in the pathogenesis of Alzheimers disease. We used high-resolution NMR to study zinc binding to amyloid beta-peptide 1-40 at physiologic pH. Metal binding induces a structural change in the peptide, which is in chemical exchange on an intermediate rate, between the apo-form and the holo-form, with respect to the NMR timescale. This causes loss of NMR signals in the resonances affected by the binding. Heteronuclear correlation experiments, N-15-relaxation and amide proton exchange experiments on amyloid beta-peptide 1-40 revealed that zinc binding involves the three histidines (residues 6, 13 and 14) and the N-terminus, similar to a previously proposed copper-binding site [Syme CD, Nadal RC, Rigby SE, Viles JH (2004) J Biol Chem279, 18169-18177]. Fluorescence experiments show that zinc shares a common binding site with copper and that the metals have similar affinities for amyloid beta-peptide. The dissociation constant K-d of ...
Effects of Nerve Growth Factor and Nitric Oxide Synthase Inhibitors on Amyloid Precursor Protein mRNA Levels and Protein Stability
Activities of Daily Living • Adaptation, Physiological • Adaptation, Psychological • Adult • African Continental Ancestry Group • Age Factors • Aged • Aged, 80 and over • Amyloid beta-Protein Precursor • Animals • Animals, Newborn • Anthropology, Physical • Anthropometry • Anxiety • Arthralgia • Behavior • Behavior, Animal • Biological Evolution • Biomechanics • Bone Density • Comorbidity • Disability Evaluation • Disabled Persons • Disease Models, Animal • Educational Status • Electromyography • Electrophysiology • Employment • Energy Metabolism • European Continental Ancestry Group • Evolution • Fear • Feeding Behavior • Female • Forearm • Fossils • Gait • Gait Disorders, Neurologic • Harmaline • Hominidae • Humans • Hyperalgesia • Imaging, Three-Dimensional • Joint Instability • Knee Joint • Life Style • Locomotion • Lumbosacral Region • Male • Mice • Mice, Inbred C57BL • Mice, Transgenic • ...
Lithium is an anti-psychotic that has been shown to prevent the hyperphosphorylation of tau protein through the inhibition of glycogen-synthase kinase 3-beta (GSK3β). We recently developed a mouse model that progresses from amyloid pathology to tau pathology and neurodegeneration due to the genetic deletion of NOS2 in an APP transgenic mouse; the APPSwDI/NOS2−/− mouse. Because this mouse develops tau pathology, amyloid pathology and neuronal loss we were interested in the effect anti-tau therapy would have on amyloid pathology, learning and memory. We administered lithium in the diets of APPSwDI/NOS2−/− mice for a period of eight months, followed by water maze testing at 12 months of age, immediately prior to sacrifice. We found that lithium significantly lowered hyperphosphorylated tau levels as measured by Western blot and immunocytochemistry. However, we found no apparent neuroprotection, no effect on spatial memory deficits and an increase in histological amyloid deposition. Aβ levels
K23620 AMBP; protein AMBP K15619 SPINT1; Kunitz-type protease inhibitor 1 K23421 SPINT2; Kunitz-type protease inhibitor 2 K23422 SPINT3; Kunitz-type protease inhibitor 3 K23423 SPINT4; Kunitz-type protease inhibitor 4 K03909 TFPI; tissue factor pathway inhibitor K23087 TFPI2; tissue factor pathway inhibitor 2 K04520 APP; amyloid beta A4 protein K08117 APLP2; amyloid-like protein 2 K23621 WFIKKN; WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein K23621 WFIKKN; WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein K23622 EPPIN; eppin K23622 EPPIN; eppin K23623 WFDC8; WAP four-disulfide core domain protein 8 K23624 PAPLN; papilin K23619 COL28A; collagen type XXVIII alpha ...
The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombins endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and

APBA2 (amyloid beta precursor protein binding family A member 2)APBA2 (amyloid beta precursor protein binding family A member 2)

... amyloid beta precursor protein binding family A member 2), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol ... amyloid beta (A4) precursor protein-binding, family A, member 2 (X11-like). ... amyloid-beta binding in utero embryonic development protein binding cytoplasm plasma membrane chemical synaptic transmission ... amyloid-beta binding in utero embryonic development protein binding cytoplasm plasma membrane chemical synaptic transmission ...
more infohttp://atlasgeneticsoncology.org/Genes/GC_APBA2.html

The Functions of the Amyloid Precursor Protein Gene and Its Derivative Peptides: I Molecular Biology and Metabolic ProcessingThe Functions of the Amyloid Precursor Protein Gene and Its Derivative Peptides: I Molecular Biology and Metabolic Processing

Analysis of the cDNA of Aβ revealed its origins from the larger precursor protein. There are at least four types of mRNA ... The amyloid precursor protein gene (APP) and its derivative peptides have important functions in the central nervous system. ... 1 Regulates the Processing of Beta-Amyloid Precursor Protein C-Terminal Fragments and the Generation of Amyloid Beta-Protein in ... W. Araki and R. J. Wurtman, "Increased Expression of Amyloid Precursor Protein and Amyloid Precursor-Like Protein 2 During ...
more infohttps://www.scirp.org/Journal/PaperInformation.aspx?PaperID=5533

High-resolution characterization of structural changes involved in prion diseases and dialysis-related amyloidosis
            ...High-resolution characterization of structural changes involved in prion diseases and dialysis-related amyloidosis ...

All of these disorders result from protein misfolding which leads to fibrillization and deposition of amyloid plaques in ... aggregation of beta-2-microglobulin (hβ2m) - the light chain of the type I major histocompatibility complex. Due to its low ... precursor ensembles on the morphology of the resulting fibrils. Furthermore, new information on solvent protection of the ... Protein aggregation is the cause of several human diseases such as diabetes mellitus type 2, Parkinson s disease, Alzheimer s ...
more infohttps://ediss.uni-goettingen.de/handle/11858/00-1735-0000-0006-AD78-D

Alzheimers Disease Research Center at UCLA, Los Angeles, California - David B. Teplow, Ph.D. - Interim Director of the UCLA...Alzheimer's Disease Research Center at UCLA, Los Angeles, California - David B. Teplow, Ph.D. - Interim Director of the UCLA...

The amyloid β-protein. In Sipe J (Ed.), Amyloid Proteins: The beta sheet conformation and disease, vol. 2, Wiley-VCH Verlag ... Studying amyloid β-protein assembly. In: Xia W, Xu H, eds. Amyloid Precursor Protein, A Practical Approach. CRC Press, Boca ... 1993) Normal cellular processing of the β-amyloid precursor protein results in the secretion of the amyloid " peptide and ... Yun S, Urbanc B, Cruz L, Bitan G, Teplow DB , Stanley HE (2007) Role of electrostatic interactions in amyloid β-protein (A beta ...
more infohttp://www.eastonad.ucla.edu/research/research-programs/item/david-teplow-phd?category_id=60

The features of bone articular lesions in dialysis-related amyloidosis (DRA) and criteria for the clinical diagnosis of DRA |...The features of bone articular lesions in dialysis-related amyloidosis (DRA) and criteria for the clinical diagnosis of DRA |...

Interestingly, it has been reported that the levels of pre-dialysis serum beta-2 microglobulin which was a precursor protein of ... The accumulation of beta 2-microglobulin and inflammatory reaction in dialysis patients accelerate the amyloid deposition [57 ... Lysine-specific cleavage of beta 2-microglobulin was extracted from amyloid stones in dialysis patients [50,51,52]. ... Bommer J, Waldherr R, Ritz E. Kidney lesions in uraemic patients and beta 2-microglobulin derived amyloid. Lancet. 1985;2:1437- ...
more infohttps://rrtjournal.biomedcentral.com/articles/10.1186/s41100-019-0205-z

Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct cellular locations.Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct cellular locations.

The beta-amyloid precursor protein (betaAPP) is a transmembrane protein that is exclusively phosphorylated on serine residues ... Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct cellular locations.. Walter J., Capell A., Hung A. ... APPssw-beta). This antibody previously established the cellular location of the beta-secretase cleavage of Swedish betaAPP as a ... European Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics. UniProt is an ELIXIR core ...
more infohttps://www.uniprot.org/citations/8999878

APBB2 amyloid beta precursor protein binding family B member 2 [Homo sapiens (human)] - Gene - NCBIAPBB2 amyloid beta precursor protein binding family B member 2 [Homo sapiens (human)] - Gene - NCBI

APBB2 amyloid beta precursor protein binding family B member 2 [Homo sapiens] APBB2 amyloid beta precursor protein binding ... The protein encoded by this gene interacts with the cytoplasmic domains of amyloid beta (A4) precursor protein and amyloid beta ... General protein information Go to the top of the page Help Preferred Names. amyloid-beta A4 precursor protein-binding family B ... mRNA and Protein(s) * NM_001166050.1 → NP_001159522.1 amyloid-beta A4 precursor protein-binding family B member 2 isoform b ...
more infohttps://www.ncbi.nlm.nih.gov/gene/323

amyloid beta precursor protein binding family A member 2 ELISA Kits | Biocompare.comamyloid beta precursor protein binding family A member 2 ELISA Kits | Biocompare.com

Compare amyloid beta precursor protein binding family A member 2 ELISA Kits from leading suppliers on Biocompare. View ... amyloid beta precursor protein binding family A member 2 ELISA Kits. Clear ... amyloid beta precursor protein binding family A member 2 ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a well- ... Bovine Amyloid beta A4 precursor protein-binding family A member 2 (APBA2) ELISA Kit ...
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APBA2 (amyloid beta precursor protein binding family A member 2)APBA2 (amyloid beta precursor protein binding family A member 2)

... amyloid beta precursor protein binding family A member 2), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol ... amyloid beta (A4) precursor protein-binding, family A, member 2 (X11-like). ... amyloid-beta binding in utero embryonic development protein binding cytoplasm plasma membrane chemical synaptic transmission ... amyloid-beta binding in utero embryonic development protein binding cytoplasm plasma membrane chemical synaptic transmission ...
more infohttp://www.atlasgeneticsoncology.org/Genes/GC_APBA2.html

Expression of amyloid beta-protein precursor mRNAs in familial Alzheimers disease. - Wellcome Centre for Integrative...Expression of amyloid beta-protein precursor mRNAs in familial Alzheimer's disease. - Wellcome Centre for Integrative...

Overexpression of APP mRNAs is therefore an unlikely explanation for the deposition of the beta-amyloid (beta/A4) peptide in ... The amyloid beta-protein precursor (APP) gene and its products are implicated in the pathogenesis of Alzheimers disease. The ... The amyloid beta-protein precursor (APP) gene and its products are implicated in the pathogenesis of Alzheimers disease. The ... Adult, Alzheimer Disease, Amyloid beta-Protein Precursor, Autoradiography, Cerebral Cortex, Hippocampus, Humans, Middle Aged, ...
more infohttps://www.win.ox.ac.uk/publications/884834

Beta-amyloid precursor protein staining of nonaccidental central nervous system injury in pediatric autopsies.  - PubMed - NCBIBeta-amyloid precursor protein staining of nonaccidental central nervous system injury in pediatric autopsies. - PubMed - NCBI

Beta-amyloid precursor protein staining of nonaccidental central nervous system injury in pediatric autopsies.. Reichard RR1, ... Immunohistochemical staining for beta-amyloid precursor protein (betaAPP) is a well-established marker of traumatic axonal ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/12866814?dopt=Abstract

WikiGenes - App - amyloid beta (A4) precursor proteinWikiGenes - App - amyloid beta (A4) precursor protein

Amyloid beta protein toxicity mediated by the formation of amyloid-beta protein precursor complexes. Lu, D.C., Shaked, G.M., ... The amyloid beta-protein precursor (APP) is proteolytically cleaved to generate the amyloid beta-protein (Abeta), the principal ... In vivo, the levels of soluble amyloid beta protein correlated with caspase-cleaved fragments of the amyloid precursor protein ... Caspase cleavage of the amyloid precursor protein modulates amyloid beta-protein toxicity. Lu, D.C., Soriano, S., Bredesen, D.E ...
more infohttps://www.wikigenes.org/e/gene/e/11820.html

Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein | PNASProtein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein | PNAS

beta/A4 amyloid is derived from the amyloid precursor protein (APP), an integral membrane protein that exists as three major ... Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein. G L Caporaso, S E Gandy, J D ... Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein. G L Caporaso, S E Gandy, J D ... Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein. G L Caporaso, S E Gandy, J D ...
more infohttps://www.pnas.org/content/89/7/3055?ijkey=68c52136c75dba3b3f10e929fdeede0fa15790a5&keytype2=tf_ipsecsha

Apba1 - Amyloid-beta A4 precursor protein-binding family A member 1 - Mus musculus (Mouse) - Apba1 gene & proteinApba1 - Amyloid-beta A4 precursor protein-binding family A member 1 - Mus musculus (Mouse) - Apba1 gene & protein

May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of AAP-beta (By similarity). ... Protein. Similar proteins. Species. Score. Length. Source. B2RUJ5. Amyloid-beta A4 precursor protein-binding family A member 1 ... Protein. Similar proteins. Species. Score. Length. Source. B2RUJ5. Amyloid-beta A4 precursor protein-binding family A member 1 ... May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of AAP-beta (By similarity).By ...
more infohttps://www.uniprot.org/uniprot/B2RUJ5

Amyloid beta (A4) precursor protein degradation products - Biology-OnlineAmyloid beta (A4) precursor protein degradation products - Biology-Online

Amyloid beta (A4) precursor protein degradation products. Debate and discussion of any biological questions not pertaining to a ... Amyloid beta (A4) precursor protein degradation products of the pathogenic role of Alzheimers disease research progress. APP ... Cutting followed by the β and γ-secretase enzyme, resulting in extracellular s APP beta, A beta (A beta 40 and A beta 42) ... resulting in excess of A beta 40 and A beta 42, the formation of A beta deposition as the core of senile plaques and disease. ...
more infohttps://www.biology-online.org/biology-forum/viewtopic.php?t=25181&p=143084&hilit=fraumeni+syndrome

Beta-Amyloid Precursor Protein, CTF-31 | rPeptideBeta-Amyloid Precursor Protein, CTF-31 | rPeptide

The 31-amino acid peptide results from the proteolytic cleavage of the C- terminus of beta-amyloid precursor protein (APP) at ... Beta-Amyloid Precursor Protein, CTF-31. ORDER ONLINE • CALL 866.753.0747 • FAX 678.753.0746 ... Beta Amyloid Peptides*Beta-Amyloid Antibodies. *Beta-Amyloid Peptides, Human, Native and Mutant, Recombinant ... Labeled Peptides & Proteins*Beta-Amyloid Labeled Peptides, Recombinant. *Beta-Amyloid Labeled Peptides, Synthetic ...
more infohttps://www.rpeptide.com/products/proteins/amyloid-precursor-protein/a-1201-1

Amyloid Precursor Protein Secretases
      - beta-Secretase
     Summary Report | CureHunterAmyloid Precursor Protein Secretases - beta-Secretase Summary Report | CureHunter

Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma ... have been identified based upon the region of amyloid protein precursor they cleave. ... Amyloid Precursor Protein Secretases (beta-Secretase). Subscribe to New Research on Amyloid Precursor Protein Secretases ... beta-Secretase; alpha-Secretase; gamma-Secretase; Secretase; APP Secretase; Amyloid Precursor Protein Secretase; Secretases; ...
more infohttp://www.curehunter.com/public/keywordSummaryD053829-Amyloid-Precursor-Protein-Secretases-beta-Secretase.do

Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-[beta] Precursor Protein/Presenilin 2 Mouse Model of...Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-[beta] Precursor Protein/Presenilin 2 Mouse Model of...

... beta] Precursor Protein/Presenilin 2 Mouse Model of Alzheimers Disease.(Research Article) by International Journal of ... Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-[ ... MLA style: "Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-[beta] Precursor Protein/Presenilin 2 Mouse ... APA style: Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-[beta] Precursor Protein/Presenilin 2 Mouse ...
more infohttps://www.thefreelibrary.com/Early+Contextual+Fear+Memory+Deficits+in+a+Double-Transgenic...-a0553759603

APS -APS March Meeting 2010 
- Event - Single Molecule Manipulation and Self-Assembly of Amyloid $\beta $/A4 Precursor Protein...APS -APS March Meeting 2010 - Event - Single Molecule Manipulation and Self-Assembly of Amyloid $\beta $/A4 Precursor Protein...

We perform a single molecule level study of the RERMS sequence of amyloid $\beta $/A4 precursor protein fragment on a clean Ag( ... Abstract: D10.00003 : Single Molecule Manipulation and Self-Assembly of Amyloid $\beta $/A4 Precursor Protein on Ag(111)*. 3:18 ... Moreover, we are able to form a well ordered two-dimensional layer of the protein fragment by increasing the deposition time. A ... The mechanical stability of individual protein fragments are checked by laterally manipulating them with the STM tip. ...
more infohttp://meetings.aps.org/Meeting/MAR10/Session/D10.3

Synthetic Human Amyloid beta (A4) Precursor Protein (aa 737-751)(CT) Blocking Peptide |  Cell SciencesSynthetic Human Amyloid beta (A4) Precursor Protein (aa 737-751)(CT) Blocking Peptide | Cell Sciences

Synthetic Human Amyloid beta (A4) Precursor Protein (aa 737-751)(CT) Blocking Peptide ... Synthetic Human Amyloid beta (A4) Precursor Protein (aa 737-751)(CT) Blocking Peptide. ...
more infohttps://www.cellsciences.com/synthetic-human-amyloid-beta-a4-precursor-protein-aa-737-751-ct-blocking-peptide

Anti-Amyloid Protein-binding Protein 2, CT (Amyloid beta Precursor Protein-binding Protein 2, APPBP2 | United States Biological...Anti-Amyloid Protein-binding Protein 2, CT (Amyloid beta Precursor Protein-binding Protein 2, APPBP2 | United States Biological...

The beta-amyloid precursor protein is a cell surface protein with signal-transducing properties, and it is thought to play a ... APPBP2 interacts with microtubules and is functionally associated with beta-amyloid precursor protein transport and/or ... Anti-Amyloid Protein-binding Protein 2, CT (Amyloid beta Precursor Protein-binding Protein 2, APPBP2 ... Product information "Anti-Amyloid Protein-binding Protein 2, CT (Amyloid beta Precursor Protein-binding Protein 2, APPBP2" ...
more infohttps://www.biomol.com/products/antibodies/primary-antibodies/general/anti-amyloid-protein-binding-protein-2-ct-amyloid-beta-precursor-protein-binding-protein-2-appbp2-a2275-95c-hrp.200

Synthetic Human Amyloid beta (A4) Precursor Protein A beta NT (aa 653-662) Peptide |  Cell SciencesSynthetic Human Amyloid beta (A4) Precursor Protein A beta NT (aa 653-662) Peptide | Cell Sciences

Synthetic Human Amyloid beta (A4) Precursor Protein A beta NT (aa 653-662) Peptide ... Synthetic Human Amyloid beta (A4) Precursor Protein A beta NT (aa 653-662) Peptide. ...
more infohttps://www.cellsciences.com/synthetic-human-amyloid-beta-a4-precursor-protein-a-beta-nt-aa-653-662-peptide-1

Nuclear localization of amyloid-beta precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysisNuclear localization of amyloid-beta precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysis

Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-beta precursor protein ... 1. The amyloidprecursor protein (APP)-binding protein Fe65 and APP processing. Open this publication in new window or tab ,, ... The amyloidprecursor protein (APP)-binding protein Fe65 and APP processing. Koistinen, Niina. Stockholm University, Faculty ... Aβ is generated by sequential cleavage of the amyloidprecursor protein (APP) by β- and then γ-secretase. However, APP can ...
more infohttp://su.diva-portal.org/smash/record.jsf?pid=diva2:1104984

Immunohistochemical Identification of Amyloid-Beta and Amyloid Precursor Protein in Alzheimers Disease Optic Nerve and Retina ...Immunohistochemical Identification of Amyloid-Beta and Amyloid Precursor Protein in Alzheimer's Disease Optic Nerve and Retina ...

Conclusions: : Both amyloid-beta (AB) and amyloid precursor protein (APP) appear to be present in AD and normal optic nerves ... Immunohistochemical Identification of Amyloid-Beta and Amyloid Precursor Protein in Alzheimers Disease Optic Nerve and Retina ... Immunohistochemical Identification of Amyloid-Beta and Amyloid Precursor Protein in Alzheimers Disease Optic Nerve and Retina ... D. Aggarwal, F. N. Ross-Cisneros, A. A. Sadun; Immunohistochemical Identification of Amyloid-Beta and Amyloid Precursor Protein ...
more infohttp://iovs.arvojournals.org/article.aspx?articleid=2363974

Myc-DDK-tagged ORF clone of Homo sapiens amyloid beta (A4) precursor protein (APP), transcript variant 5 as transfection-ready...Myc-DDK-tagged ORF clone of Homo sapiens amyloid beta (A4) precursor protein (APP), transcript variant 5 as transfection-ready...

... precursor protein (APP), transcript variant 5 as transfection-ready DNA - 10 µg - OriGene - cdna clones ... Myc-DDK-tagged ORF clone of Homo sapiens amyloid beta (A4) ... Myc-DDK-tagged ORF clone of Homo sapiens amyloid beta (A4) ... home , products , origene , myc-ddk-tagged orf clone of homo sapiens amyloid beta (a4) precursor protein (app), transcript ... Myc-DDK-tagged ORF clone of Homo sapiens amyloid beta (A4) precursor protein (APP), transcript variant 5 as transfection-ready ...
more infohttps://www.bioscience.co.uk/product~186193
  • S. S. Sisodia, E. H. Koo, P. N. Hoffman, G. Perry and D. L. Price, "Identification and Transport of Full-Length Amyloid Precursor Proteins in Rat Peripheral Nervous System," Journal of Neuroscience, Vol. 13, 1993, pp. 3136-3142. (scirp.org)
  • The 50 % reduction in phenylalanine and tyrosine in HIP brains is significant given their role in supporting brain chemistry as a precursor for catecholamines (dopamine, norepinephrine, epinephrine), which may contribute to the increased morbidity and mortality in diabetics at a multi-system level beyond the effects on glucose metabolism. (springer.com)
  • When APP molecules occupy a lipid raft region of membrane, they are more accessible to and differentially cleaved by beta secretase, whereas APP molecules outside a raft are differentially cleaved by the non-amyloidogenic alpha secretase. (wikipedia.org)
  • Α-secretase pathway: (1), also known as non-amyloid formation routes. (biology-online.org)
  • 2) β-secretase pathway: also known as amyloid formation routes. (biology-online.org)
  • Addressing both, we applied intravitreally a beta secretase (BACE) inhibitor in an AD mouse model (SwAPP/Psen1d9), and investigated possible clearance pathways for Aβ. (arvojournals.org)
  • APP is cleaved either by beta-secretase or by alpha-secretase to initiate amyloidogenic (release of A beta) or nonamyloidogenic processing of APP, respectively. (uni-muenchen.de)
  • Thus, access of alpha- and beta-secretase to APP, and therefore A beta generation, may be determined by dynamic interactions of APP with lipid rafts. (uni-muenchen.de)
  • alpha secretase and beta secretase both remove nearly the entire extracellular domain to release membrane-anchored carboxy-terminal fragments that may be associated with apoptosis. (wikipedia.org)
  • Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed. (uniprot.org)
  • PS2M1 mice express human PS2 proteins containing the N141I mutation on a C57BL/6JJcl background (purchased from Immuno-Biological Laboratories Co, Ltd., Fujioka, Japan) [22, (thefreelibrary.com)
  • After 8 days retina samples of adult SwAPP/Psen1d9 and wild-type C57BL/6 mice (healthy wt controls) were embedded in paraffin or were lysed for protein analyses. (arvojournals.org)
  • Formalin-fixed, paraffin-embedded 5µm sections of 30 optic nerves and retinas from 15 donors previously diagnosed with AD and 30 age-matched control optic nerves and retinas from 15 individuals with no AD, other neurodegenerative diseases, diabetes mellitus, or sepsis were stained with antibodies reactive against amyloid-beta (AB) and amyloid precursor protein (APP). (arvojournals.org)
  • Both amyloid-beta (AB) and amyloid precursor protein (APP) appear to be present in AD and normal optic nerves and retinas. (arvojournals.org)
  • A beta generation was dependent on endocytosis and was reduced after expression of the dynamin mutant K44A and the Rab5 GTPase-activating protein, RN-tre. (uni-muenchen.de)
  • Recent studies implicate human amylin aggregates cause proteotoxicity (cell death induced by misfolded proteins) in both the brain and the heart. (springer.com)
  • In particular, similarities in post-translational processing have invited comparisons to the signaling role of the surface receptor protein Notch. (wikipedia.org)
  • This increase is augmented by simultaneous treatment with the protein phosphatase inhibitor okadaic acid. (pnas.org)
  • APBB2 is associated with amphetamine use and plasma beta-amyloids in patients receiving methadone maintenance treatment. (nih.gov)
  • This work opens possibilities of using well ordered protein structures on inorganic surfaces for future bimolecular electronic and nano-bio applications. (aps.org)
  • Antibody cross-linking dramatically increased production of A beta in a cholesterol-dependent manner. (uni-muenchen.de)