Mutation amyloid precursor protein secretases. Medical search. Frequent questions

Mutations in APP are associated with familial forms of early onset Alzheimer's disease as well as with Cerebral Amyloid Angiopathy (CAA). (alzforum.org)
MAPT encodes the microtubule associated protein tau, a protein central to Alzheimer's disease neuropathology. (alzforum.org)
More than 300 mutations in PSEN1 have been reported and mutations in PSEN1 are the most common cause of early onset Alzheimer's disease. (alzforum.org)
Missense mutations in PSEN2 are a rare cause of early onset Alzheimer's disease. (alzforum.org)
Amyloid beta (Aβ or Abeta) denotes peptides of 36-43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. (wikipedia.org)
The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold. (wikipedia.org)
Aβ is the main component of amyloid plaques, extracellular deposits found in the brains of people with Alzheimer's disease. (wikipedia.org)
Research suggests that soluble oligomeric forms of the amyloid beta may be causative agents in the development of Alzheimer's disease. (wikipedia.org)
The "amyloid hypothesis" - that the plaques are responsible for the pathology of Alzheimer's disease - is accepted by the majority of researchers, but is not conclusively established. (wikipedia.org)
The β-amyloid (Aβ) peptide is the major constituent of amyloid plaques in Alzheimer's disease (AD) brain and is likely to play a central role in the pathogenesis of this devastating neurodegenerative disorder. (jneurosci.org)
The amyloid β-protein precursor and Alzheimer's disease. (url.edu)
Alzheimer's disease (AD) is triggered by the pathophysiological cleavage of a single transmembrane glycoprotein denominated amyloid β-protein precursor (AβPP) rendering amyloid β-peptide (Aβ) that aggregates in β-sheets forming the neuritic plaques. (url.edu)
Profundice en los temas de investigación de 'The amyloid β-protein precursor and Alzheimer's disease. (url.edu)
Although the amyloid precursor protein (APP) and its proteolysis are regarded as key elements of the pathology of Alzheimer's disease, the physiological function of APP is not well understood and mice lacking App and the related gene Aplp2 die early postnatally without any obvious histopathological abnormalities. (phoenixpeptide.com)
Identification of the Alzheimer's disease amyloid precursor protein (APP) and its homologue APLP2 as essential modulators of glucose and insulin homeostasis and growth. (phoenixpeptide.com)
The amyloid precursor protein (APP), the source of the neurotoxic amyloid beta (A beta) peptide involved in Alzheimer's disease (AD), belongs to a conserved family of related proteins. (phoenixpeptide.com)
Research in Dr. Thinakaran's lab investigates mechanisms that regulate Alzheimer's disease β-amyloid (Aβ) production and deposition. (curealz.org)
For over twelve years heI has been leading a group at the University of Chicago, investigating multiple aspects of Alzheimer's disease cell biology including, the physiological and pathological functions of presenilins, regulation of APP trafficking and metabolism, modulation of amyloid production/deposition by post-translational modification of APP secretases and interaction with associated proteins, and the characterization of subcellular sites and membrane microdomains involved in the generation of Aβ peptides. (curealz.org)
Familial Alzheimer's disease (fAD) mutations alter amyloid precursor protein (APP) cleavage by γ-secretase, increasing the proportion of longer amyloidogenic amyloid-β (Aβ) peptides. (nature.com)
The amyloid precursor protein being cleaved by gamma and beta secretases and releasing the amyloid beta peptide, which can accumulate to amyloid plaques, one of the main symptoms of Alzheimer's disease. (jax.org)
Missense mutations in the presenilins cause familial Alzheimer's disease by augmenting the γ-secretase cleavage of APP and overproducing one of the proteolytic derivatives, the Aβ peptide. (hku.hk)
2017. Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzheimer's disease. (ocl-journal.org)
2000. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. (ocl-journal.org)
2010. Adeno-associated virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimer's disease. (ocl-journal.org)
According to the amyloid hypothesis , the amyloid plaques that form between the brain's neurons as it ages are toxic and hence cause the cognitive losses associated with Alzheimer's . (mcgill.ca)
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the most cases of dementia, which is characterized by the deposition of dense plaques of amyloid beta (Aβ) plaques and neurofibrillary tangles consisting of hyperphosphorylated tau. (oncotarget.com)
In Alzheimer's disease (AD), the accumulation and deposition of amyloid-β (Aβ) peptides in the brain is a central event. (elsevierpure.com)
Alzheimer's possesses complex pathologies of heterogeneous nature counting proteins as one major factor along with enzymes and mutated genes. (benthamscience.com)
[6] APP is best known as the precursor molecule whose proteolysis generates amyloid beta (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 Alzheimer's disease patients. (handwiki.org)
Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause familial susceptibility to Alzheimer's disease. (handwiki.org)
A mutation (A673T) in the APP gene protects against Alzheimer's disease. (handwiki.org)

APP encodes amyloid precursor protein, a transmembrane protein which is cleaved to form amyloidogenic Aβ peptides. (alzforum.org)
Pathogenic mutations generally alter processing by secretases, leading in an overall increase in Aβ production and/or a change in the ratio of specific Aβ peptides. (alzforum.org)
The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. (wikipedia.org)
The plaques are composed of a tangle of Aβ oligomers and regularly ordered aggregates called amyloid fibrils, a protein fold shared by other peptides such as the prions associated with protein misfolding disease, also known as Proteinopathy. (wikipedia.org)
It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. (curehunter.com)
A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES. (curehunter.com)
The plaques mainly consist of beta-amyloid (Aβ) peptides, which are generated through cleavage of the amyloid precursor protein (APP) by secretases, such as beta-site APP-cleavage enzyme 1 (BACE1). (biologists.com)
Senile plaques are composed of aggregations of small peptides called β-amyloid (Aβ). (biomedcentral.com)
Extracellular neuritic plaques are deposits of differently sized small peptides called β-amyloid (Aβ) that are derived via sequential proteolytic cleavages of the β-amyloid precursor protein (APP) [ 6 ]. (biomedcentral.com)
This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. (antibodypedia.com)
Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. (antibodypedia.com)
Certain proteins, or certain peptides (which are short proteins) fold in space into special structures known as beta-pleated sheets. (mcgill.ca)
AD is pathologically characterized by the deposition of pathogenic Aβ peptides that are derived from larger integral membrane proteins, termed β-amyloid precursor proteins (APPs). (jneurosci.org)
Build up of harmful amyloid- (A) peptides is definitely thought to be at the core of AD pathogenesis [2]C[4]. (moca-09.org)

Aβ can also form the deposits that line cerebral blood vessels in cerebral amyloid angiopathy. (wikipedia.org)
Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). (antibodypedia.com)

Increasing evidence suggests that amyloid-β peptide, a hallmark of AD, may disrupt axonal transport and in so doing, contribute to AD pathophysiology. (semcs.net)
And it is the high content of beta-pleated sheets in the protein (peptide) that Glenner was investigating that accounts for its affinity for Congo red and thioflavin-in short, for its amyloid nature. (mcgill.ca)
Because the peptide that Glenner identified had never been described previously, he named it A-beta peptide (A for amyloid and beta for the beta-pleated sheets). (mcgill.ca)
We now know that A-beta peptide, also commonly known as beta-amyloid , comes from the cleavage of another, larger protein called amyloid protein precursor(APP). (mcgill.ca)
For the beta-amyloid peptide to be released, APP must be cleaved at two locations by two special types of enzymes. (mcgill.ca)
Then gamma-secretases make another cut, this time inside the cell membrane, thus releasing the beta-amyloid peptide. (mcgill.ca)
NIHMS376099-product-03.docx (65K) GUID:?002EEEF9-2510-4DC6-9257-CDF8E7Abdominal55DB Abstract The proteolytic control of amyloid Rabbit Polyclonal to OR52E2 precursor protein (APP) to generate purchase Tedizolid the neurotoxic A peptide is central to the pathogenesis of Alzheimer disease (AD). (researchensemble.com)
The key pathological changes observed in AD brain tissue are amyloid beta (Aβ) peptide deposited and neuritic plaques, hyperphosphorylated tau protein and neurofibrillary tangles [ 4 , 5 ]. (oncotarget.com)
AD is a neurodegenerative disorder, characterized by progressive brain deposition of the amyloid β peptide (Aβ), which is generated by proteolytic cleavage of amyloid precursor protein (APP) by β- and γ-secretases. (biomedicineandprevention.com)

assessed amyloid deposition in AD mouse models (5xFAD and APP NLGF , respectively) crossed with mice showing minor structural myelin defects driven by the lack of myelin-proteins like CNP (CNP -/- ) or PLP (PLP -/y ). 5XFAD mice harbor five familial AD (FAD) mutations triggering Aβ overproduction, and already exhibit amyloid deposition two months after birth (4). (biologists.com)
This indicates that chronic and acute myelin dysfunction trigger amyloid deposition and reveals myelin defects as a risk factor for plaque formation. (biologists.com)
This indicates that absence of myelin delays amyloid deposition. (biologists.com)
It is commonly assumed that these deficits arise due to β-amyloid accumulation and plaque deposition. (springer.com)
Pathological hallmarks of AD include the presence of hyperphosphorylated tau and amyloid protein deposition. (frontiersin.org)

Amyloid plaques contain both Aβ40 and Aβ42, while vascular amyloid is predominantly the shorter Aβ40. (wikipedia.org)
An alternative hypothesis is that amyloid oligomers rather than plaques are responsible for the disease. (wikipedia.org)
Nevertheless, the pathological hallmarks of extracellular amyloid beta (Aβ) enriched plaques and intracellular neurofibrillary tangles of hyper-phosphorylated tau are shared between fAD and sporadic AD (sAD). (nature.com)
Therefore, the presence of beta amyloid plaques alone is not sufficient to cause disease, and after a certain stage, their elimination is probably not sufficient to slow its course. (jax.org)
The characteristic features of AD pathology are amyloid plaques, neurofibrillary tangles and loss of neuronal connections in the brain (1). (biologists.com)
Light-sheet microscopy analysis revealed that 6-month-old CNP -/- 5xFAD and PLP1 -/y 5xFAD double mutants exhibited a higher load of amyloid plaques than 5xFAD mice. (biologists.com)
Similarly, induction of experimental autoimmune encephalomyelitis (EAE) - a model for chronic immune-mediated myelin loss - caused the formation of amyloid plaques in the spinal cord of 5xFAD mice. (biologists.com)
For the next several decades, scientists tried in vain to determine exactly which protein formed the central component of what were now being called amyloid plaques. (mcgill.ca)
It was not until 1984 that American research pathologist George Glenner and his team characterized the structure of the protein molecules that agglutinate to form amyloid plaques. (mcgill.ca)
The two main forms of beta-amyloid have 40 and 42 amino acids, respectively, and the latter is the one that has the greater propensity to agglutinate and thereby form amyloid plaques . (mcgill.ca)
Characteristic to the disease is the profound atrophy of the brain accompanied by amyloid-beta (Aβ) plaques and the presence of tau neurofibrillary tangles (NFTs). (frontiersin.org)
The neuropathologic hallmarks of AD are senile plaques composed of extracellular deposits of amyloid-β (Aβ) and neurofibrillary tangles composed of intracellular aggregates of tau protein with multiple post-translational modifications including phosphorylation. (biomedcentral.com)
Senile plaques are complicated and heterogeneous lesions that contain not only amyloid deposits and tau positive neurites, but also neurites with degenerating pre- and post-synaptic elements (so-called dystrophic neurites), as well as activated microglia and reactive astrocytes [ 1 ]. (biomedcentral.com)
Amyloid-β is also a major constituent of senile plaques. (biomedicineandprevention.com)

Significant efforts have been focused on the mechanisms responsible for Aβ production, including the proteolytic enzymes gamma- and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein). (wikipedia.org)
Since AβPP is playing a key role in AD development, this review will be focused in the structure, proteolytic processing, related secretases, mutations, localization and physiological role of AβPP protein. (url.edu)
Austin SA, Combs CK (2008) Mechanisms of microglial activation by amyloid precursor protein and its proteolytic fragments. (springer.com)

Familial AD (FAD) cases are caused by autosomal dominant mutations in the genes for amyloid precursor protein (APP) and the presenilins (PS1 and PS2) ( Sisodia and St George-Hyslop, 2002 ). (jneurosci.org)
Here we show that glutamatergic neurons differentiated from ESCs lacking both genes reveal a decreased expression of the vesicular glutamate transporter 2 (VGLUT2) both at the mRNA and protein level, as well as a reduced uptake and/or release of glutamate. (phoenixpeptide.com)
fAD-causing mutations in the genes coding for amyloid precursor protein ( APP ), presenilin 1 ( PSEN1 ) and presenilin 2 ( PSEN2 ) affect the production of Aβ in the central nervous system (CNS), implicating altered APP cleavage and processing in the AD disease mechanism [ 1 ]. (nature.com)
Also, researchers found that rare mutations in any one of three genes involved with beta amyloid production or accumulation leads to early-onset AD in nearly everyone who has them. (jax.org)
Genetic association of AD with 451 polymorphisms in 15 genes encoding retromer or retromer-associated proteins was tested inside a Caucasian sample of 8,309 AD instances and 7,366 cognitively normal elders using individual SNP and gene-based checks. (researchensemble.com)
The first milestone with linkage analysis revealed the mutations in APP, PSEN1, and PSEN2 genes that cause EOAD. (oncotarget.com)
But pathogenic mutations in these three genes can only explain a small fraction of EOAD families. (oncotarget.com)
Although mutations in APP, PS1, or PS2 cause early-onset familial AD, ABCA7 encoding ATP-binding cassette transporter A7 is one of the susceptibility genes for late-onset AD (LOAD), in which its loss-of-function variants increase the disease risk. (elsevierpure.com)

Embryonic stem cell-derived neurons as a cellular system to study gene function: lack of amyloid precursor proteins APP and APLP2 leads to defective synaptic transmission. (phoenixpeptide.com)
Using five control induced pluripotent stem cell (iPSC) lines and seven iPSC lines generated from fAD patients, we investigated the effects of mutations on the Aβ secretome in human neurons generated in 2D and 3D. (nature.com)
Axonal amyloid precursor protein expressed by neurons in vitro is present in a membrane fraction with caveolae-like properties. (ocl-journal.org)
Aβ is cleaved from amyloid precursor protein (APP) by β-secretase and γ-secretase mainly in neurons. (elsevierpure.com)
Interestingly, ABCA7 deletion facilitated the processing of APP to Aβ by increasing the levels of β-site APP cleaving enzyme 1 (BACE1) and sterol regulatory element-binding protein 2 (SREBP2) in primary neurons and mouse brains. (elsevierpure.com)
Knock-down of ABCA7 expression in neurons caused endoplasmic reticulum stress highlighted by increased level of protein kinase R-like endoplasmic reticulum kinase (PERK) and increased phosphorylation of eukaryotic initiation factor 2α (eIF2α). (elsevierpure.com)
Amyloid-beta precursor protein ( APP ) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons . (handwiki.org)

As a post-doctoral fellow, at The Johns Hopkins University School of Medicine Dr. Thinakaran participated in the early characterization of presenilin biology and investigations on how FAD mutations in PS1 affect Aβ production using cell culture and animal models. (curealz.org)
Whereas, distinct presenilin 1 ( PSEN1 ) mutations lead to either (2) reduced γ-secretase activity, (3) altered protein stability or (4) reduced PSEN1 maturation, all culminating in reduced γ-secretase carboxypeptidase-like activity. (nature.com)
Presenilin 1 (PS1), presenilin 2, and nicastrin form high molecular weight complexes that are necessary for the endoproteolysis of several type 1 transmembrane proteins, including amyloid precursor protein (APP) and the Notch receptor, by apparently similar mechanisms. (hku.hk)

Cleavage of APP by two proteases, the β- and γ-secretases, is required to liberate Aβ from APP ( Tanzi and Bertram, 2005 ). (jneurosci.org)
Mutations in the AβPP sequence or in the secretases that cleavage AβPP determinate an early onset of AD. (url.edu)
1) APP V717I mutations alter γ-secretase cleavage site preference. (nature.com)
Null mutations in PS1 inhibit both γ-secretase cleavage of APP and S3-site cleavage of the Notch receptor. (hku.hk)
This substitution is adjacent to the beta secretase cleavage site and results in a 40% reduction in the formation of amyloid beta in vitro. (handwiki.org)

MAPT mutations are not linked to familial forms of AD, but can cause frontotemporal dementia (FTD) and several other tauopathies. (alzforum.org)
Sometimes the failure happens when a sorting motif is definitely mutated C a notable example becoming the mutation of the NPXY motif identified as causal in familial hypercholesterolemia by Brown and Goldstein [3]. (researchensemble.com)
Background: A mutation in the BRI2/ITM2b gene causes familial Danish dementia (FDD). (elsevierpure.com)

10%) of AD cases result from an inherited autosomal dominant gene mutation and have an early-onset (the fourth to sixth decade). (biomedcentral.com)

The abnormal aggregation and accumulation of neurotoxic Aβ has been proposed as the primary driving force for AD in the amyloid hypothesis. (biomedicineandprevention.com)

Specifically, they study the biology of BACE1 and γ-secretase, the two enzymes that sequentially cleave amyloid precursor protein (APP) to generate Aβ. (curealz.org)
The endocytic system mediates the processing of APP by controlling its access to secretases that cleave APP. (researchensemble.com)
Hence, one of the main targets of novel disease-modifying drugs is definitely to minimize the brain A load by focusing on the - and -secretases that cleave the amyloid precursor protein (APP) to generate A [5]. (moca-09.org)

This resembles the β-amyloid precursor protein (APP) in Alzheimer disease (AD), which can be physiologically processed by α-, β-, and γ-secretases. (mdpi.com)
Almkvist O, Basun H, Wagner SL, Rowe BA, Wahlund LO, Lannfelt L (1997) Cerebrospinal fluid levels of alpha-secretase-cleaved soluble amyloid precursor protein mirror cognition in a Swedish family with Alzheimer disease and a gene mutation. (springer.com)
Barger SW, Harmon AD (1997) Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature 388:878-881. (springer.com)
There has been a growing gratitude recently of the importance of right protein sorting in regulating the control of amyloid precursor protein (APP) and therefore the proteins that function in mediating localization to the post-Golgi endocytic system have been of great interest to studies of the underlying causes of late-onset Alzheimer disease (AD). (researchensemble.com)

investigated the impact of severe reduction of cortical myelin on amyloid pathology. (biologists.com)

2013. Palmitoylation of amyloid precursor protein regulates amyloidogenic processing in lipid rafts. (ocl-journal.org)

There is evidence that microglia form a protective barrier around amyloid aggregates to prevent further Aβ accumulation (2). (biologists.com)
Although this copper chelator could possibly interfere with plaque formation, Cuprizone-treated mice showed a substantial increase of amyloid aggregates in regions of strong demyelination. (biologists.com)

However the central sequence KLVFFAE is known to form amyloid on its own, and probably forms the core of the fibril. (wikipedia.org)

For one thing, the accumulation of beta amyloid in the brains of patients has been one of the few known disease hallmarks. (jax.org)

Nevertheless, there is a strong correlation between the neurotoxicity caused by prion proteins and the blockade of their normal proteolysis. (mdpi.com)

The human cellular prion protein (PrP C ) is a glycosylphosphatidylinositol (GPI) anchored membrane glycoprotein with two N-glycosylation sites at residues 181 and 197. (mdpi.com)
To investigate the APP in vivo interactome in an unbiased manner, we generated mice that harbor a mouse prion protein promoter-driven cDNA encoding human APP-695 fused to a C-terminal affinity tag. (jneurosci.org)

The pathogenic mutations, which can be either exonic or intronic, generally alter the relative production of tau isoforms and lead to changes in microtubule assembly and/or the propensity of tau to aggregate. (alzforum.org)

Cholesterol-related disorders have been associated with sEH, which plays an important role in the metabolism of cholesterol precursors. (frontiersin.org)
Cholesterol metabolism in the brain is independent of peripheral tissues due to the blood-brain barrier (BBB) that impairs the entrance of the protein-bound lipid into the central nervous system (CNS). (frontiersin.org)

Recent investigations in their lab center on the regulation of BACE1 and γ-secretase function by post-translational S-palmitoylation, live-cell analysis of dynamic membrane trafficking of BACE1, and the characterization of γ-secretase modulating protein p23. (curealz.org)
Aβ is liberated from type I integral membrane proteins, termed β-amyloid precursor proteins (APPs), by the concerted action of β-secretase (BACE1) and γ-secretase (for review, see Selkoe, 2002 ). (jneurosci.org)

Therefore, instead of focusing on rare cases of early-onset disease caused by specific genetic mutations, scientists are taking a look at the bigger picture. (jax.org)

In mammals, the APP family contains amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2). (phoenixpeptide.com)
This review discusses the function of sEH in mammals and its protein structure and catalytic activities. (frontiersin.org)
This review aims to summarize the role of sEH in mammals and its protein structure and catalytic activities. (frontiersin.org)
[10] Homologous proteins have been identified in other organisms such as Drosophila (fruit flies), C. elegans (roundworms), [11] and all mammals . (handwiki.org)

Here, we reviewed the physiological/pathological roles and therapeutic significance of nearly all the proteins associated with AD that addresses putative as well as probable targets for developing effective anti-AD therapies. (benthamscience.com)

Our results also suggest that the biological role of membrane-anchored StARkin family protein is to protect eukaryotic cells from triterpenes glycosylated at the C-3 position. (bvsalud.org)
Molecular dynamics simulations and surface hydrophobicity mapping of both proteins in different media showed that RTA rearranges its structure in a membrane-like environment much more efficiently than MLA. (bvsalud.org)
A single-pass type I membrane protein. (curehunter.com)
APP is a transmembrane protein, which means that the APP molecule passes through the neuron's cell membrane. (mcgill.ca)
First, beta-secretases cut the APP's chain of amino acids at a certain distance outside the cell membrane. (mcgill.ca)
A key mediator of APP localization is definitely SorL1 C a membrane protein that has been genetically linked to AD. (researchensemble.com)
The retromer complex is definitely a conserved protein complex required for endosome-to-Golgi retrieval of a number of physiologically important membrane proteins including SorL1. (researchensemble.com)
We display that Snx3 and Rab7A proteins interact with the cargo-selective retromer complex through independent mechanisms to regulate the membrane association of retromer and therefore are key mediators of retromer function. (researchensemble.com)
1. Intro The localization of membrane proteins to discrete and specific compartments within eukaryotic cells is definitely governed by a complex interplay of protein-protein relationships in which a sorting motif(s) in the cytoplasmic tail of a membrane protein is definitely identified by membrane-associated coating proteins to direct the respective membrane proteins into a tubule or vesicle for transport to another compartment. (researchensemble.com)
Using this tag, we prepared mild detergent lysates from transgenic mouse brain cortical membrane preparations and isolated a number of previously identified APP-interacting proteins. (jneurosci.org)
[12] The amyloid beta region of the protein, located in the membrane-spanning domain, is not well conserved across species and has no obvious connection with APP's native-state biological functions. (handwiki.org)

Thus, this study demonstrates that using proteomic methods on our transgenic model can uncover important in vivo APP-interacting proteins that will provide insights into the biology of APP. (jneurosci.org)
Thus, this study demonstrates that our transgenic model can uncover important in vivo APP-interacting proteins that will contribute to our understanding of APP processing in in vivo settings. (jneurosci.org)

The glymphatic system clears metabolic waste from the mammalian brain, and in particular amyloid beta. (wikipedia.org)
Why did everyone focus for so long on lessening beta amyloid buildup for AD therapy? (jax.org)
But what if the damage had already been done, and decreasing beta amyloid at that stage of disease progression was too late? (jax.org)
The findings raise the possibility that blocking beta amyloid is simply not a viable target for therapy. (jax.org)
Researchers now think that beta amyloid buildup is only one part of a much larger collection of processes that lead to AD progression. (jax.org)
Therefore, effective experimental platforms are vital for investigating the genetic variants that affect AD risk, the environmental and behavioral factors such as diet and exercise that play a role over time, and the interplay between beta amyloid, tau, the immune system, brain vasculature and other potential contributors to disease. (jax.org)
Abramov E, Dolev I, Fogel H, Ciccotosto GD, Ruff E, Slutsky I (2009) Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. (springer.com)
2003. Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor protein. (ocl-journal.org)
These beta-pleated sheets are also what makes this protein so compact, stable, and insoluble. (mcgill.ca)
APP, like the beta-amyloid that is derived from it, is thus a normal component of the organism. (mcgill.ca)
Amyloid-beta precursor protein is an ancient and highly conserved protein . (handwiki.org)
We then went on to demonstrate significant reductions in amyloid beta (Aβ) levels after AAV-based delivery of VHH-B9 into the CNS of a mouse model of cerebral amyloidosis. (biorxiv.org)

Here, we show that APP can coimmunoprecipitate NEEP21 from nontransgenic mouse brain and from mammalian cells stably coexpressing both proteins. (jneurosci.org)

In an attempt to understand the function of APP, in vitro studies have focused on the identification of interacting proteins. (jneurosci.org)

The addition of an affinity tag allowed us to avoid the use of antibodies targeted toward the intracellular C-terminal tail of APP, a region to which a number of reported interacting proteins bind ( King and Turner, 2004 ). (jneurosci.org)

Aβ deposits within the walls of blood vessels in the form of amyloid angiopathy are found in many patients with AD, but it is also found in other neurologic disorders [ 2 ]. (biomedcentral.com)

All fAD mutation lines demonstrated an increased Aβ42:40 ratio relative to controls, yet displayed varied signatures for Aβ43, Aβ38, and short Aβ fragments. (nature.com)

BRI2 is an inhibitor of amyloid- precursor protein (APP) processing, which is genetically linked to Alzheimers disease (AD) pathogenesis. (elsevierpure.com)

Our results indicate a significant functional role of APP and amyloid precursor-like protein 2 (APLP2) in the development of synaptic function by the regulation of glutamatergic neurotransmission. (phoenixpeptide.com)
Purification of APP-AT protein complexes and identification of the constituents by mass spectrometry revealed several previously reported APP-interacting proteins as well as proteins involved in synaptic maintenance. (jneurosci.org)
Disturbed expression of these proteins results in synaptic dysfunction, cognitive impairment, memory loss, and neuronal degradation. (benthamscience.com)
HSPs, which ameliorate oxidative stress, calpains, which help in regulating synaptic plasticity, and calmodulin-like skin protein (CLSP) with its neuroprotective role are few promising future targets for developing anti-AD therapies. (benthamscience.com)

Novel research horizons for presenilins and gamma-secretases in cell biology and disease. (ocl-journal.org)

Anatomy23

Organisms8

Diseases12

Chemicals and Drugs54

Analytical, Diagnostic and Therapeutic Techniques and Equipment21

Psychiatry and Psychology3

Phenomena and Processes49

Disciplines and Occupations1

Humanities1

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Peptides14

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Peptide9

Deposition5

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Cleavage5

Familial3

Autosomal dominant1

Hypothesis1

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BACE12

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Membrane11

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