• However, these genes can not account for the overall inheritance of susceptibility to POAG pathogenesis. (molvis.org)
  • Genetics plays an important role in PD, with disease-susceptibility loci including more than 90 genes, including SNCA (Synuclein Alpha), LRRK2 (Leucine Rich Repeat Kinase 2), GBA (Glucosylceramidase Beta) , and MAPT (Microtubule Associated Protein Tau) [ 4 ]. (nature.com)
  • DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease. (nature.com)
  • The critical next step will be to definitively identify the responsible genes and understand their functions in both health and disease. (texaschildrens.org)
  • Despite the promise of current human genetic methods, such as genome-wide association studies, they often fail to identify disease susceptibility genes with certainty, instead highlighting broad genomic regions. (texaschildrens.org)
  • We are taking advantage of the rapid and powerful genetics available in the fruit fly Drosophila melanogaster in order to accelerate the validation of responsible genes and an understanding of their functions in disease pathogenesis. (texaschildrens.org)
  • We are testing candidate human susceptibility genes for functional genetic interactions in these fly models of neurodegeneration. (texaschildrens.org)
  • This identified approximately 140 chromosome loci where nucleotides deviated from the reference sequence GRCh37 hg19 comprising the three genes TRPV1, LTB4R and LTB4R2. (researchgate.net)
  • 2020) provided a detailed review of the genes involved in different forms of ALS with FTD, noting that common disease pathways involve disturbances in RNA processing, autophagy, the ubiquitin proteasome system, the unfolded protein response, and intracellular trafficking. (beds.ac.uk)
  • Genetic Heterogeneity of Amyotrophic Lateral Sclerosis ALS is a genetically heterogeneous disorder, with several causative genes and mapped loci. (beds.ac.uk)
  • Nature Genetics) of the first new susceptibility genes for 17 years defined a pivotal moment in Alzheimer's genetics research. (cardiff.ac.uk)
  • What is striking about her group's findings is that the genes identified show patterns of relationship, which implicate novel disease mechanisms, including immunity, endocytosis, lipid transport and ubiquination. (cardiff.ac.uk)
  • Genes responsible for familial AD include the amyloid precursor protein ( APP ), presenilin 1 ( PS1 ) and presenilin 2 ( PS2 ), whereas the main genes responsible for familial FTLD are microtubule-associated protein tau gene ( MAPT ) and progranulin ( GRN ). (touchneurology.com)
  • Advances in genomic technologies and statistical methods have converged to allow the discovery of susceptibility loci for complex genetic traits, and the field now confronts the enormous challenge to confirm the responsible genes and define their functions in the biology of health and disease. (bcm.edu)
  • In addition to the potential for fundamental biological insights, functional dissection of susceptibility genes will be essential to realize the full promise of human genetics for clinical applications. (bcm.edu)
  • Most notably, rare pathogenic mutations have been identified in the amyloid precursor protein, microtubule associate protein tau, and alpha-synuclein genes, encoding the primary constituents of the defining disease pathologies (amyloid plaques and Tau neurofibrillary tangles in AD, and Lewy bodies in PD, respectively). (bcm.edu)
  • Mutations in three genes coding for the amyloid precursor protein ( APP ), presenilin 1 ( PS-1 ), and presenilin 2 ( PS-2 ) account for most cases of early onset, autosomal dominant familial AD (FAD), but only for 2% of all the AD cases. (bmj.com)
  • In humans, MHC proteins are encoded by the Human Leukocyte Antigen (HLA), a group of more than 200 genes located closely together on the short arm of chromosome 6. (antibodies-online.com)
  • The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. (springer.com)
  • The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions and carbon monoxide. (springer.com)
  • Genetic association studies aimed at defining susceptibility to POAG may provide important insights into the pathogenesis of POAG. (molvis.org)
  • This review focuses on the current knowledge of the pathogenesis of the inflammatory and neurodegenerative elements of the multiple sclerosis plaque. (researchgate.net)
  • Multiple genome-wide association studies (GWAS) over the past 10 years have uncovered more than 200 loci that independently contribute to disease pathogenesis. (researchgate.net)
  • Evidence for CD4 + T-cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4 + T lymphocytes is summarized to support the thesis that calcitriol is sunlight's main protective signal transducer in autoimmune disease risk. (frontiersin.org)
  • In humans, IL-13Ralpha1 lies within the PARK12 locus of susceptibility to Parkinson's disease and may have a role in the pathogenesis of this neurodegenerative disease. (cusabio.com)
  • Despite this evidence, the BSCB (like the BBB) breakdown in disease pathogenesis remains unclear [ 6 , 7 ]. (hindawi.com)
  • Aberrant expression of many specific lncRNAs was reported to be correlated to the pathogenesis of various diseases in human and model animals [ 16 , 17 ]. (researchsquare.com)
  • Expression of human amyloid-beta, Tau, or alpha-synuclein proteins in the fly nervous system recapitulates many core features of Alzheimer's disease and Parkinson's disease pathogenesis. (texaschildrens.org)
  • DNA Methylation Signature of Aging: Potential Impact on the Pathogenesis of Parkinson's Disease. (neurotree.org)
  • The production of Aβ, which represents a crucial step in AD pathogenesis, is the result of the cleavage of a bigger precursor, named amyloid precursor protein (APP), which is overexpressed in AD. (touchneurology.com)
  • It has been suggested that miRNA binding sites on WFS1 play a critical role in the regulation of the wolframin protein, and loss of WFS1 function may lead to the pathogenesis of diabetes. (bvsalud.org)
  • In the past 2 decades, genome-wide association studies (GWAS) have identifyed genetic susceptibility loci that confer the risk for sporadic PD [ 3 ]. (biomedcentral.com)
  • Although there has been much success in identifying genetic variants associated with common diseases using genome-wide association studies (GWAS), it has been difficult to demonstrate which variants are causal and what role they have in disease. (researchgate.net)
  • Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS), but not with other autoimmune conditions such as rheumatoid arthritis, psoriasis and Crohn's disease. (researchgate.net)
  • Hence, our study demonstrates that clinical practice can be informed by comparing GWAS across common autoimmune diseases and by investigating the functional consequences of the disease-associated genetic variation. (researchgate.net)
  • AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. (uni-luebeck.de)
  • Specifically, we utilized genotype and phenotype data from n = 931 individuals collected under the auspices of the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study to perform a total of 19 separate GWAS analyses. (uni-luebeck.de)
  • In summary, our study highlights the power of using quantitative endophenotypes as outcome traits in AD-related GWAS analyses and nominates several new loci not previously implicated in cognitive decline. (uni-luebeck.de)
  • In the past, genome-wide association studies (GWAS) have identified an important number of risk loci associated with AD pathology 3 , but a causal relationship remains difficult to establish. (nature.com)
  • 2012). We have also contributed to genome-wide association studies (GWAS) seeking novel susceptibility loci for AD neuropathologic traits, including amyloid neuritic plaques and Tau neurofibrillary tangles. (bcm.edu)
  • The MAPT gene, encoding the microtubule-associated protein tau on chromosome 17q21.31, is result of an inversion polymorphism, leading to two allelic variants (H1 and H2). (biomedcentral.com)
  • In the first study Alison Goate of Washington University and her colleagues identified a region on chromosome 10 that appears to contain a risk factor and concluded that the Alzheimer's susceptibility gene in this region could be as influential as the apolipoprotein E (APOE) gene on chromosome 19. (scientificamerican.com)
  • The third report, in contrast, provides evidence of an Alzheimer's locus in a different area of the chromosome. (scientificamerican.com)
  • Rudoph E. Tanzi of Harvard Medical School and his colleagues concentrated on chromosome stretches near the gene that makes insulin degrading enzyme, which may also play a role in degrading so-called amyloid beta protein. (scientificamerican.com)
  • 6 The gene is located at chromosome 21q21.22 and encodes for a transmembrane protein that is normally processed into amyloid fragments. (touchneurology.com)
  • Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22. (sagepub.com)
  • Although possession of the ε4 allele of the apolipoprotein E gene appears to be an important biological marker for Alzheimer's disease (AD) susceptibility, strong evidence indicates that at least one additional risk gene exists on chromosome 12. (bmj.com)
  • This paper provides a brief presentation on the genetics of multiple sclerosis susceptibility and on current work that uncovers the cellular effects, immunological and non-immunological, associated with genetic risk variants. (researchgate.net)
  • Moreover, the modest contribution that these variants make to disease risk has raised questions regarding their medical relevance. (researchgate.net)
  • As with many other complex diseases, risk of developing MS is driven by multiple common variants whose biological effects are not immediately clear. (researchgate.net)
  • The clinical manifestation of neurodegenerative disease is the culmination of a multi-tiered pathogenic cascade that evolves over decades-understanding how genetic variants impact this causal chain is essential. (texaschildrens.org)
  • NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases. (texaschildrens.org)
  • For instance, the SwissVariant database (http://swissvar.expasy.org/) contained 76 613 variants in 20 244 human proteins on 10 January 2018. (deepdyve.com)
  • We show that ALS heritability is enriched in splicing variants and in binding sites of 6 RNA-binding proteins including TDP-43 and FUS. (cdc.gov)
  • In the coming years, with the completion of the largest possible genetic meta-analyses along with the advent of whole-genome sequencing, our knowledge of common and rare susceptibility variants will rapidly expand, implicating vast genetic networks including hundreds of loci in neurologic diseases. (bcm.edu)
  • Substantial evidence supports a model in which many genetic variants promote the development of neuropathology, subsequently leading to the clinical manifestations of disease. (bcm.edu)
  • The study also emphasizes the significant role the ethnic background may play in determining the effect of genetic variants on susceptibility to metabolic diseases. (bvsalud.org)
  • Farnesyltransferase inhibitors (FTIs) have recently been investigated for repositioning toward the treatment of neurodegenerative disorders and block the action of farnesyltransferase (FTase) to catalyze farnesylation, a post-translational modification that regulates proteins involved in lysosome function and microtubule stability. (biomedcentral.com)
  • These studies take advantage of murine models relevant to neurodevelopmental disorders, Parkinson and Huntington diseases, and depression . (igbmc.fr)
  • Recent advances have made the discovery of genetic susceptibility loci for complex human phenotypes a reality, including nervous system disorders. (texaschildrens.org)
  • We focus on Alzheimer's disease and Parkinson's disease, two incurable neurodegenerative disorders and experimental paradigms for the age-dependent failure of brain cognitive and motor control in humans. (texaschildrens.org)
  • Molecular genetics of neurodegenerative disorders (e.g. (helsinki.fi)
  • The current understanding of ALS and FTD is that some forms of these disorders represent a spectrum of disease with converging mechanisms of neurodegeneration. (beds.ac.uk)
  • Until recently, our understanding of the genetic causes for human diseases were largely limited to the study of extreme phenotypes produced by Mendelian disorders. (bcm.edu)
  • Scholz SW, Bras J. Genetics underlying atypical parkinsonism and related neurodegenerative disorders. (jamanetwork.com)
  • Post-translational modifications (PTMs) play important roles in regulating several human diseases, like cancer, neurodegenerative disorders, and metabolic disorders. (bvsalud.org)
  • Inheritance of the TNF-α (−863) C allele has been associated with an elevated risk of Alzheimer disease. (molvis.org)
  • The neuronal injuries associated with Alzheimer disease have several similarities with the optic nerve changes often seen with POAG. (molvis.org)
  • Alzheimer disease (AD) is the most common progressive degenerative form of dementia, strongly associated with advancing age. (medscape.com)
  • Although Alzheimer disease (AD) is more frequent in individuals with Down syndrome (DS), the main contributing factor is unknown. (medscape.com)
  • Alzheimer disease (AD) is the most common form of dementia. (medscape.com)
  • The reason why Alzheimer disease (AD) is more frequent in individuals with Down syndrome (DS) is not known. (medscape.com)
  • The disease was originally described by Alois Alzheimer and Gaetano Perusini in 1906, and it is clinically characterised by progressive cognitive impairment including impaired judgement, decision-making and orientation, often accompanied, in later stages, by psychobehavioural disturbances as well as language impairment. (touchneurology.com)
  • 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)
  • Introduction: Synaptic dysfunction and degeneration is one of the earliest events in Alzheimer's disease (AD) and the best correlate of cognitive decline. (lu.se)
  • Alzheimer's disease (AD) is the most common cause of dementia. (lu.se)
  • Researchers are thus scrambling to identify risk factors for this neurodegenerative disorder and understand the biological mechanisms by which the disease unfolds, in hopes that this information will lead to improved treatment and prevention. (scientificamerican.com)
  • It was reported that K630A mutation in androgen receptor has been shown to cause a loss of acetylation site and has been implicated in Kennedy's disease, an inherited neurodegenerative disorder [8]. (deepdyve.com)
  • Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. (beds.ac.uk)
  • ALS is sometimes referred to as 'Lou Gehrig disease' after the famous American baseball player who was diagnosed with the disorder. (beds.ac.uk)
  • Alzheimer's disease (AD) is the most common cause of dementia in the elderly, whereas frontotemporal lobar degeneration (FTLD) is the most frequent neurodegenerative disorder with a pre-senile onset. (touchneurology.com)
  • Alzheimer's disease (AD) is a progressive neurodegenerative disorder that occurs predominantly in later life. (bmj.com)
  • As detailed on our website, the G&E Program tackles foundational questions in development and disease that can be grouped into five research areas: epigenetics, developmental genetics, human genetics, cancer genetics, and genome maintenance and repair. (uth.edu)
  • Mutations are associated with mitochondrial dysfunction, leading to neuronal death in Parkinson's disease and aberrant metabolism in tumourigenesis. (wikipedia.org)
  • A key neuropathological hallmark of PD are neuronal inclusions positive for the protein α-synuclein known as Lewy bodies and Lewy neurites. (nature.com)
  • Both are also characterised by an accumulation of protein aggregates resulting in progressive neuronal loss, suggesting a common underlying pathology. (ukessays.com)
  • At week 24, those receiving tofersen showed a reduction in concentrations of toxic SOD1 protein and markers of neuronal injury. (cdc.gov)
  • Neuronal gene expression profiling: uncovering the molecular biology of neurodegenerative disease. (sagepub.com)
  • 7] analyzed amino acid variations of 15 different PTMs and indicated that about 4.5% of amino acid variations may affect protein function through disruption of PTMs, and the mutation of 238 PTMs sites in human proteins was causative of disease. (deepdyve.com)
  • The Wolfram syndrome 1 gene (WFS1) is the main causative locus for Wolfram syndrome, an inherited condition characterized by childhood-onset diabetes mellitus, optic atrophy, and deafness. (bvsalud.org)
  • In recent years, it has been revealed that Parkinson's disease pathology may begin to manifest in the gastrointestinal track at a much earlier time point than in the brain. (nature.com)
  • A complementary approach directly leverages the underlying disease pathology as an intermediate trait, or endophenotype. (bcm.edu)
  • The goal is to understand how discrete developmental events contribute to physiological diversity in cognitive performance, or affective susceptibility to stress, and understand the neurodevelopmental basis of neurologic diseases. (igbmc.fr)
  • Our research integrates genetic investigation in human subjects and model organisms, with the goal of understanding brain function and aging, and improving the treatment of neurologic disease. (texaschildrens.org)
  • Homozygosity for the more common haplotype H1 is associated with an increased risk for several tauopathies, but also for the synucleinopathy Parkinson's disease (PD). (biomedcentral.com)
  • Recent investigations identified some loci, namely INPP5D, CD2AP and CASS4 that mediate AD susceptibility and are high-incidence risk factors in AD [18-20]. (bioerc-iend.org)
  • citation needed] Mutations in this gene are known to cause a familial form of Parkinson's disease known as autosomal recessive juvenile Parkinson's disease (AR-JP). (wikipedia.org)
  • 1997), a protein whose gene (SYN, aka PARK 1) has been linked to familial PD (Athanassiadou et al. (ukessays.com)
  • We find that PM20D1 is a methylation and expression quantitative trait locus coupled to an AD-risk associated haplotype, which displays enhancer-like characteristics and contacts the PM20D1 promoter via a haplotype-dependent, CCCTC-binding-factor-mediated chromatin loop. (nature.com)
  • To understand the multifaced aspects of Parkinson's disease, it may be desirable to expand the complexity of these models, to include different brain regions, vasculature, immune cells as well as additional diverse organ-specific organoids such as gut and intestine. (nature.com)
  • Enhanced mTORC1 signaling and protein synthesis in pathologic α-synuclein cellular and animal models of Parkinson's disease. (neurotree.org)
  • The c-Abl inhibitor IkT-148009 suppresses neurodegeneration in mouse models of heritable and sporadic Parkinson's disease. (neurotree.org)
  • Cell Biology of Parkin: Clues to the Development of New Therapeutics for Parkinson's Disease. (neurotree.org)
  • Parkinson's Disease (PD) is characterized clinically by tremors at rest, bradykinesia (slowness of voluntary movement), muscle rigidity, decrease in postural reflex and facial expression and an altered gait (Kumar et al. (ukessays.com)
  • Something similar happens in Parkinson's disease, but this time you need to block Cav1.3. (epiphanyasd.com)
  • AD and Parkinson's disease, ALS, schizophrenia) and complex statistical analyses (e.g. gene-wide/burden, pathway analyses). (cardiff.ac.uk)
  • Primary open angle glaucoma (POAG) is a multifactorial neurodegenerative disease. (molvis.org)
  • Primary open angle glaucoma (POAG), the most common form of glaucoma in the Western world, is an age-related, complex disease characterized by progressive irreversible degeneration of the optic nerve due to apoptotic retinal ganglion cell death [2] . (prolekarniky.cz)
  • In the present study, we aimed to clarify whether the MAPT haplotype influences expression of MAPT and SNCA , encoding the protein α-synuclein (α-syn), on mRNA and protein levels in postmortem brains of PD patients and controls. (biomedcentral.com)
  • mRNA and protein levels of MMP-9 were determined by qRT-PCR and ELISA, respectively. (bvsalud.org)
  • Apolipoprotein E (APOE) is a lipid-transport protein abundantly expressed in most neurons in the central nervous system. (dovepress.com)
  • Understanding the mutations in APOE, their structural properties, and their isoforms is important to determine its role in various diseases and to advance the development of therapeutic strategies. (dovepress.com)
  • Targeting APOE may be a potential approach for diagnosis, risk assessment, prevention, and treatment of various neurodegenerative and cardiovascular diseases in humans. (dovepress.com)
  • 2 In the blood, APOE protein could interact with lipids, resulting in lipoproteins, including very-low-density lipoproteins (VLDL). (dovepress.com)
  • APOE is also involved in the formation of chylomicrons and VLDL and affects the activity of other lipid metabolism-associated proteins and enzymes, such as hepatic lipase and lipoprotein lipase. (dovepress.com)
  • Concerning sporadic AD, it is known that the presence of the ε4 allele of the apolipoprotein E gene is a susceptibility factor. (touchneurology.com)
  • Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). (prolekarniky.cz)
  • Research in G&E labs is broadly focused on the fundamental genetic, epigenetic, and genomic mechanisms that control cell growth and differentiation, and that cause cancer and other human diseases. (uth.edu)
  • Indeed, "functional and mechanistic work on the molecular etiology of disease remains one of the major challenges in modern biology" ( 5 ). (frontiersin.org)
  • We also participate in collaborative studies for the functional genetic dissection of Alzheimer's disease, focusing on the responsible neuropathology, amyloid neuritic plaques and Tau neurofibrillary tangles. (texaschildrens.org)
  • To increase the utilization of current computational resources, we 﫿rst provide an overview of computational prediction of amino acid variations that influence protein PTMs and their functional analysis. (deepdyve.com)
  • All the proposed and approved treatments aim to slow a patient's rate of functional decline and prolong life, but reversing damage in neurodegenerative conditions is a more elusive goal. (cdc.gov)
  • Nrf2 consists of six functional Neh domains (Neh1-Neh6), from which, the amino-terminal Neh2 domain controls binding Keap1-the inhibitor protein Kelch-like ECH-associated protein 1, that is responsible for the cytosolic sequestration of Nrf2 under physiological conditions (Fig. 2 a). (springer.com)
  • In particular, parkin recognises proteins on the outer membrane of mitochondria upon cellular insult and mediates the clearance of damaged mitochondria via autophagy and proteasomal mechanisms. (wikipedia.org)
  • posttranslational modifications, amino acid variations, computational mutation analysis, protein PTM predictor, network biology Introduction Protein PTMs are biochemical alterations of amino acids that change the physicochemical properties of target proteins, leading to structural changes and therefore regulating protein-protein interactions and cellular signal transduction in developmental and cancer pathways [1]. (deepdyve.com)
  • The mammalian target of the rapamycin (mTOR) signaling pathway is another key player in regulating cellular processes and its dysregulation is linked to several diseases including type 2 diabetes (T2D). (bvsalud.org)
  • 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)
  • Oxidative stress generated during such stressful conditions may damage DNA and proteins, and as a consequence the cellular processes are disturbed. (springer.com)
  • Importantly, TNF-blocking drugs can promote onset or exacerbation of MS, but they have proven highly efficacious in the treatment of autoimmune diseases for which there is no association with rs1800693. (researchgate.net)
  • This review highlights recent advances in vitamin D and T-lymphocyte biology in an effort to harness vitamin D's potential to reduce the impact of autoimmune diseases. (frontiersin.org)
  • Autoimmune diseases represent a failure of self-identification leading to an immune-mediated assault on host tissues. (frontiersin.org)
  • We drew mainly on MS and T1D research because intensive investigation has generated detailed insights into vitamin D mechanisms in these diseases and provided valuable guidance for research on other autoimmune diseases. (frontiersin.org)
  • Other autoimmune diseases are included where robust mechanistic data exist. (frontiersin.org)
  • A recent chapter ( 6 ) and a review ( 7 ) have summarized vitamin D mechanisms in autoimmune diseases more generally. (frontiersin.org)
  • We have ongoing interests in the systems level analysis and reconstruction of regulatory networks, inference of enhancer-promoter contacts, predictive models of gene expression and integration of three-dimensional chromatin structure with one-dimensional epigenetic measurements in the context of cancer, malaria, asthma and several autoimmune diseases. (ucsd.edu)
  • All recognized mutations for AD are associated with increased deposition of amyloid-beta (Abeta), a peptide fragment comprising 39-43 amino acids that derive from the catabolism of the amyloid precursor protein (APP) molecule. (medscape.com)
  • There are a number of cases in which mutations of the modified sites were found to be involved in disease. (deepdyve.com)
  • Research into the gene mutations discovered in such hereditary cases has also contributed to the understanding of the aetiology of the spontaneous, late onset form of the disease. (ukessays.com)
  • Animal models of the disease, created using neurotoxins such as rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or transgenic mice that overexpress human SYN gene (for ï ¡-synuclein) mutations, do not faithfully replicate the structure and antigenicity of the Lewy bodies found in PD (Dickson 2001). (ukessays.com)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • The results indicate that several of the proteins included in the panel may serve as synaptic biomarkers for AD. (lu.se)
  • We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. (lu.se)
  • Alzheimer's disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, aging populations. (uni-luebeck.de)
  • Interstitial lung disease caused by storage of sphingomyelin in pulmonary macrophages results in frequent respiratory infections and often respiratory failure. (beds.ac.uk)
  • Parkin is a 465-amino acid residue E3 ubiquitin ligase, a protein that in humans and mice is encoded by the PARK2 gene. (wikipedia.org)
  • in humans and mice indicate, for the first time, a role of interleukin-13 receptor alpha1 in myocardial homeostasis and heart failure and suggests a new therapeutic target to treat heart disease. (cusabio.com)
  • In fact, all three studies suggest that this newly discovered genetic influence may affect the processing of amyloid beta protein, a peptide important in the formation of the amyloid plaques found in the brains of Alzheimer's patients. (scientificamerican.com)
  • Aβ disrupts microtubules in presynaptic dystrophic neurites, resulting in the accumulation of impaired endolysosomal and autophagic organelles transporting β-site amyloid precursor protein cleaving enzyme (BACE1). (biomedcentral.com)
  • b) some microRNAs and proteins (microglobulins, interleukins) related to a common network with amyloid precursor protein and tau [15]. (bioerc-iend.org)
  • The amyloid cascade hypothesis of Advertisement shows that, in Advertisement, abnormalities occur through the secretion from the amyloid precursor proteins (APP), resulting in an unbalance between clearance and creation of the [23, 37]. (bioerc-iend.org)
  • and further, our genome scan implicates common variation in the amyloid precursor protein (APP) gene (Shulman et al. (bcm.edu)
  • The main pathological features of AD are characterised by neurofibrillary tangles and senile plaques caused by the progressive deposition of Aβ peptides in the brain, composed mainly of 39-43 peptides generated by proteolytic cleavage of the Aβ precursor protein (APP). (bmj.com)
  • Goran MI, Ball GDC, Cruz ML. Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. (medigraphic.com)
  • Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. (prolekarniky.cz)
  • Since then, the consortium she leads, GERAD (Genetic and Environmental Risk in Alzheimer's Disease), has continued the momentum and has played a leading role in further discoveries. (cardiff.ac.uk)
  • Our strategy has recently identified cell adhesion converging on the cytoskeleton as likely important for Tau-mediated neurodegeneration and Alzheimer's disease susceptibility, and we are now following up these insights to elucidate the detailed mechanisms. (texaschildrens.org)
  • In this regard, comprehensive studies of the impact of amino acid variation on protein PTMs will be helpful for further understanding of how genetic polymorphisms are involved in regulating biological and pathological processes and providing instructive information for drug development of various related diseases. (deepdyve.com)
  • Theoretical representations that simulate the behavior or activity of biological processes or diseases. (lookformedical.com)
  • The amino acid changes could alter the protein charge and stability, inducing distinct physiological functions. (dovepress.com)
  • however, the protein is a component of a multiprotein E3 ubiquitin ligase complex which in turn is part of the ubiquitin-proteasome system that mediates the targeting of proteins for degradation. (wikipedia.org)
  • Both genetic and environmental factors are thought to contribute to the pathophysiology of the disease. (molvis.org)
  • Since rodent models cannot recapitulate many of the human disease features, human induced pluripotent stem cells derived from Parkinson's patients have been used to generate brain organoids, greatly contributing to our understanding of the disease pathophysiology. (nature.com)
  • Epigenetic regulation in the pathophysiology of Alzheimer's disease. (nature.com)
  • The latter diseases CBD and PSP are clinically characterized as atypical Parkinson syndromes [ 15 ]. (biomedcentral.com)
  • This indicates that the clinical experience with these drugs parallels the disease association of rs1800693, and that the MS-associated TNFR1 variant mimics the effect of TNF-blocking drugs. (researchgate.net)
  • Correspondingly, the clinical strategies available for the management of the disease have widened. (researchgate.net)
  • Since its early clinical development, it has held great promise for the treatment of MMe, where it seems to act mainly as a cytostatic agent, thus stabilizing the disease. (kanker-actueel.nl)
  • Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility. (lu.se)
  • To address these questions, we use genetic, pharmacological or behavioral mouse models of specific diseases, as well as CRISPR- and viral-based approaches to control gene expression. (igbmc.fr)
  • Many observations point to a major role for classical HLA loci in determining susceptibility to viral infections 1 . (antibodies-online.com)
  • Tau hypothesis [33-35] postulates that this excessive or abnormal phosphorylation of Tau protein and its transformation into PHF-Tau (paired helical filament) and NFT-Tau (neurofibrillary tangles) precedes AD. (bioerc-iend.org)
  • The IL-13R A(1) +1398 A/G polymorphism does not contribute to asthma or allergic rhinitis susceptibility. (cusabio.com)
  • This +1071 T/A polymorphism was not associated with the disease, although it may weakly modulate the impact of the +1073 C/T polymorphism. (bmj.com)
  • however, many individuals have IOP elevation without optic nerve disease [6] , and at least 33% of affected individuals have progressive retinal ganglion cell loss despite IOP measurements in the normal range (less than 22 mmHg), a condition defined as normal-pressure glaucoma (NPG) [7] . (prolekarniky.cz)
  • The amino acid variation S326C of human OGG1 disrupts Ser-326 phosphorylation site and affects susceptibility to a variety of cancers [9]. (deepdyve.com)
  • sIL13ralpha1 as a circulating human protein with an unexpected role in glucose metabolism. (cusabio.com)
  • Human liver protein map: a reference database established by microsequencing and gel comparison. (drugbank.com)
  • Fig. 1: Overview of the PM20D1 locus and its relation to AD in human frontal cortex. (nature.com)
  • This difference in permeability has attracted motor neuron disease (MND) research, with findings suggesting that the BSCB is damaged in human and rodent ALS sufferers. (hindawi.com)
  • Protein expression and function of organic anion transporters in short-term and long-term cultures of Huh7 human hepatoma cells. (cancerindex.org)
  • Classical class I and class II Human Leukocyte Antigen (HLA) are leading candidates for infectious disease susceptibility. (antibodies-online.com)
  • Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2. (antibodies-online.com)
  • There exists a multitude of E3 ligases, which differ in structure and substrate specificity to allow selective targeting of proteins to intracellular degradation. (wikipedia.org)