• An interdisciplinary and integrative research approach to identify the cell networks and meditators of the brain and systemic immune and inflammatory systems is expected to give greater insight into the etiological mechanisms underlying Alzheimer's disease. (nih.gov)
  • The goal of this FOA is to establish the role of the brain innate immune system, the systemic immune system, and the crosstalk and changes with age between the two in the development and progression of Alzheimer's disease. (nih.gov)
  • Alzheimer's disease (AD) is the leading cause of dementia in those over the age of 65. (nih.gov)
  • Alzheimer's disease (AD) is a neurodegenerative, irreversible and progressive disease that leads to memory loss and dementia. (fapesp.br)
  • Currently, 2-3% of the population over 65 years of age are living with Parkinson's disease (PD), making this disorder the most prevalent late-onset neurodegenerative disorder worldwide after Alzheimer's disease. (nature.com)
  • The largest international study ever conducted on Alzheimer's disease, the I-GAP (International Genomics Alzheimer s Project) consortium has identified eleven new regions of the genome involved in the onset of the disease. (neurodegenerationresearch.eu)
  • These 11 new confirmed genes can open new avenues in the understanding of the occurrence of Alzheimer's disease. (neurodegenerationresearch.eu)
  • Conversely, ATXN1 loss-of-function is involved in Alzheimer's disease (AD) and tumorigenesis. (biomedcentral.com)
  • The activity of almost 2,000 genes varied with age, including genes in pathways related to neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. (nih.gov)
  • Rubinstein-Taybi syndrome and Fetal Alcohol Spectrum Disorder, cancer, neurodegenerative diseases including Huntington's Disease, Alzheimer's Disease, Parkinson's Disease and Amyotrophic Lateral Sclerosis, cardiac hypertrophy, asthma and inflammation, as well as memory impairment and cognitive dysfunction. (nih.gov)
  • In the aging Western society, acute brain damage and chronic neurodegenerative conditions such as Alzheimer's and Parkinson's diseases are amongst the most debilitating diseases, affecting hundreds of millions of people worldwide. (neurodegenerationresearch.eu)
  • Unfortunately, increased longevity is accompanied by a rise in the incidences of age-related diseases such as Alzheimer's disease (AD). (frontiersin.org)
  • Alzheimer's disease (AD) is the 6th leading cause of death in the US and affects more than 35 million people worldwide ( Alzheimer's Disease International, 2014 ). (frontiersin.org)
  • Alzheimer's disease (AD) is the most common form of dementia affecting the growing aging population today, with prevalence expected to rise over the next 35 years. (frontiersin.org)
  • The growth in life expectancy and the developing aging population has led to the increased prevalence of chronic diseases, such as Alzheimer's disease (AD). (frontiersin.org)
  • Alzheimer's disease is a heterogeneous disease and has multiple cognitive subtypes. (frontiersin.org)
  • The variant of AD in which visual symptoms are prominent due to the localized pathology in the parieto-occipital region is often referred to as visual variant Alzheimer's disease (VVAD) ( 13 ). (frontiersin.org)
  • Following Alzheimer's disease, Parkinson's disease (PD) is the second-most common neurodegenerative disorder in the United States. (nih.gov)
  • In fiscal years 2013 and 2014, the percentage increase allocated to NIA was higher than that allocated to NIH overall, but the bulk of that increase reflects a substantial increase in research dollars for Alzheimer's Disease (AD). (nih.gov)
  • The link is more compelling in neurodegenerative disorders such as Alzheimer's, Huntington's, Parkinson's and amyotrophic lateral sclerosis (ALS). (springer.com)
  • If you've spent time with individuals affected with Alzheimer's disease (AD), you might have noticed that some people lose their memory and other cognitive skills more slowly than others. (nih.gov)
  • This suggests that the protein, called TREM2, and the immune system as a whole, may be promising targets to help fight Alzheimer's disease. (nih.gov)
  • Background: Genetic studies have been highly successful in identifying genetic regions associated with Alzheimer's disease, and we are now at the exciting juncture of applying this knowledge to understanding disease mechanisms. (wustl.edu)
  • https://adsp-fgc.niagads.org/) aims to apply cutting-edge genomics technologies, high-throughput genetic screening and cutting edge disease modeling to understand the functional consequences of genetic susceptibility and resilience to Alzheimer's Disease, and to identify genetics-guided targets for the prevention, diagnosis, and treatment of Alzheimer's disease and related dementias (AD/ADRD). (wustl.edu)
  • The first lead structures that affect neurite outgrowth or A42 aggregation will serve as the basis for new strategies to promote neuronal regeneration (e.g. after injury) or to treat Alzheimer's disease. (europa.eu)
  • 12. Identification of novel drug targets for Alzheimer's disease by integrating genetics and proteomes from brain and blood. (nih.gov)
  • Mitochondrial dysfunction is a feature of neurodegenerative diseases, including Alzheimer's disease (AD). (biomedcentral.com)
  • Alzheimer's Disease (AD) is a chronic progressive neuro-degenerative disorder affecting cognitive functioning and reducing life expectancy. (atomictherapy.org)
  • Based on disease progression, symptoms and its severity Alzheimer's Disease can be divided into 4 stages which are progressive worsening of symptoms in same continuum. (atomictherapy.org)
  • Late-Onset Alzheimer's Disease (LOAD) is a leading form of dementia. (biomedcentral.com)
  • We conducted systematic comparisons of representative Machine Learning models for predicting LOAD from genetic variation data provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. (biomedcentral.com)
  • An estimate from Ballard [ 3 ] shows that Alzheimer's Disease affects between 4 and 6 percent of the population around 65 years old, that the incidence of the disease doubles every five years after 65 years of age, and by age of 85 between 30%-50% is affected by some form of AD. (biomedcentral.com)
  • New technologies in genome editing with site-specific nucleases will also play a powerful role in our ability to create and validate new disease genes and allelic variants associated with human ALS. (medscape.com)
  • Results: We identified 19 551 rare variants in 806 genes related to oncological diseases, among them 89% have been located in non-coding regions. (bvsalud.org)
  • The etiology of AD is complex, but mutations in at least four loci were associated with increased susceptibility to AD, although these genes do not account for the majority of cases. (fapesp.br)
  • Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. (nature.com)
  • They also suggest new candidate genes and pathways that may be involved in disease risk. (neurodegenerationresearch.eu)
  • GTEx was designed to sample as many tissues as possible from a large number of individuals in order to understand the causal effects of genes and variants, and which tissues contribute to predisposition to disease," says Dr. Emmanouil Dermitzakis at the University of Geneva Faculty of Medicine, Switzerland, a coauthor of the main Science paper. (nih.gov)
  • During differentiation, these bivalent chromatin marks are typically resolved, correlating with transcriptional activation of tissue-specific genes and concomitant silencing of gene loci associated with alternative developmental pathways. (nih.gov)
  • These have uncovered many novel aspects of disease biology (e.g. autophagy in IBD) and several of the genes these studies identified are now the targets of drugs undergoing clinical trials for the treatment of immune-mediated disorders. (sanger.ac.uk)
  • As a series of biomarkers, the human leukocyte antigen genes with its related proteomics play cortical roles on the antigen presentation of major histocompatibility complex molecules to stimulate the differentiation of T lymphocytes and i-proteasome activities under their immune response to the PD-related environmental alteration and genetic variation. (biomedcentral.com)
  • Our knowledge of how the immune system contributes to PD pathogenesis is constantly evolving, with increasing evidence for a role of several genes and susceptibility loci. (staycured.com)
  • Therefore, various susceptibility genes and environmental factors are believed to be involved in the aetiology of TLE, which is considered to be a heterogeneous, polygenic, and complex disorder. (hindawi.com)
  • This QTL atlas will be used to perform colocalization and identify the functional genes within AD risk loci, and Mendelian Randomization to identify novel causal genes, proteins and druggable targets. (wustl.edu)
  • By initially focusing on 20 disease relevant genes and by selecting three key levels of analytical complexity, EUROSPIN defined a very substantial 'parameter space' of projects, which was further extended by adding several additional disease genes and mutants to the EUROSPIN portfolio in the course of its activities. (europa.eu)
  • DLGs), to analyses of the role and disease-relevant dysfunction of individual genes at all envisioned analysis levels - from molecular and cellular studies, via behavioral analyses, to studies in neuronal networks (e.g. (europa.eu)
  • The pilot/large-scale projects may be for SNPs that are located throughout the genome or that are located in particular genome regions or in sets of genes related to particular processes, organs, or diseases. (nih.gov)
  • The team demonstrated that eQTLs can boost the ability to detect associations with genetically complex disorders such as hypertension. (nih.gov)
  • Epigenetic drugs exist at various stages of development for the treatment of cancer, psychiatric disorders, obesity, and other complex diseases. (nih.gov)
  • Dysregulation of these pathways is thus associated with many pathological processes, including neurodegenerative diseases, metabolic disorders, and cancer. (mdpi.com)
  • Brain transcriptomic profiling reveals common alterations across neurodegenerative and psychiatric disorders. (upf-csic.es)
  • Based on the characteristic protein conformation and function, central nervous degenerative diseases involved in movement disorders can be clinically classed as α-synucleinopathy, Tauopathy and TDP-43 proteinopathy in which PD belongs to α-synucleinopathy [ 2 ]. (biomedcentral.com)
  • Several primary neurodegenerative disorders distinct from Parkinson's disease (PD) share parkinsonian features of bradykinesia, rigidity, tremor, and balance disturbances. (medscape.com)
  • These disorders have complex clinical presentations that reflect degeneration in various neuronal systems. (medscape.com)
  • Indeed, dysregulation of the UPS or autophagy is linked to several neurodegenerative, infectious and inflammatory disorders as well as cancer. (springer.com)
  • However, it remains unclear if neuronal antigen presentation plays a role in PD or other neurodegenerative disorders, and efforts are underway to better understand the potential impact of autoimmune responses on neurodegeneration. (staycured.com)
  • Art then joined Mayo Clinic's Clinician Investigator Program, where he did clinical training in internal medicine and gastroenterology, and post-doctoral work with Dr. Gianrico Farrugia, a world leader in gastrointestinal physiology & pathophysiology, and focused on ion channel mechanosensitivity and precision medicine in functional GI disorders, which are common and complex gut-brain disorders, with nearly half of patients having disruptions in gastrointestinal mechanosensation. (nih.gov)
  • As disease progresses further the severity of symptoms of cognitive disorders of memory, thinking, reasoning increases so as to easily becoming evident and establish diagnosis of AD and excluding other condition based on slow and gradually and progressively deteriorating cognition especially in front of memory. (atomictherapy.org)
  • In addition, the disease is characterized by productive and negative symptoms, neurocognitive disorders, and impaired social adaptation. (consortium-psy.com)
  • The present data indicate, intrinsic properties of macrophages can overcome the limitations of current common therapies, tricor background screening alleviate and reverse the symptoms, and may ultimately service the quality of life of patients with various neurodegenerative disorders. (centralparkcarriagesofficial.org)
  • Mutations are associated with mitochondrial dysfunction, leading to neuronal death in Parkinson's disease and aberrant metabolism in tumourigenesis. (wikipedia.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)
  • Parkinson's disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. (nature.com)
  • Increased gut permeability, inflammation, and colonic α-synuclein pathology are present in early Parkinson's disease (PD) and have been proposed to contribute to PD pathogenesis. (nih.gov)
  • Two new publications outline a transformative approach to defining, studying and treating Parkinson's disease. (neurodegenerationresearch.eu)
  • Rather than approaching Parkinson's disease as a single entity, the international cadre of researchers advocates targeting therapies to distinct „nodes or clusters" of patients based on specific symptoms or molecular features of their disease. (neurodegenerationresearch.eu)
  • Diagnostic investigations are limited, and physicians rely on clinical examination and exclusion of differential diagnoses that may cause cognitive impairment, such as depression, Parkinson's disease (PD), hypothyroidism, drug interactions, and vitamin deficiencies ( 6 ). (frontiersin.org)
  • Most recently, the NINDS held the "Parkinson's Disease 2014: Advancing Research, Improving Lives" conference, which resulted in a series of prioritized recommendations that will inform ongoing and future efforts in PD research. (nih.gov)
  • Parkinson's disease (PD) is referring to the multi-systemic α-synucleinopathy with Lewy bodies deposited in midbrain. (biomedcentral.com)
  • The raised incidence of Parkinson's disease (PD) becomes a serious issue in an aged society [ 1 ]. (biomedcentral.com)
  • For more information, see the Medscape Reference article Parkinson's Disease . (medscape.com)
  • In this special supplement to the Journal of Parkinson's Disease , "The Immune System in Parkinson's Disease," experts highlight the latest research breakthroughs on the links between immune activation and neuroinflammation and Parkinson's disease (PD) and discuss the challenges and novel therapeutic strategies targeting the immune system with the hope of reducing or reversing neurodegeneration. (staycured.com)
  • Parkinson's disease (PD) and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. (nihr.ac.uk)
  • Mutations in leucine-rich repeat kinase 2 ( LRRK2 ) and glucocerebrosidase ( GBA ) represent two most common genetic causes of Parkinson's disease (PD). (biomedcentral.com)
  • Purpose The Oxford Parkinson's Disease Centre (OPDC) Discovery Cohort magnetic resonance imaging (MRI) sub-study (OPDC-MRI) collects high quality multimodal brain MRI together with deep longitudinal clinical phenotyping in patients with Parkinson's, at-risk individuals and healthy elderly participants. (medrxiv.org)
  • In addition to typical motor dysfunction (parkinsonism), diverse non-motor symptoms (NMS) are frequently observed in patients with Parkinson's disease (PD). (touchneurology.com)
  • The degeneration of the dopaminergic nigrostriatal system and parkinsonism (rest tremor, rigidity, bradykinesia, and postural instability/gait disorder) represent only one aspect of Parkinson's disease (PD), a multifaceted and complex disorder. (touchneurology.com)
  • Recent large-scale genome-wide association studies (GWASs) have identified multiple genetic loci associated with AD risk ( Table 124-1 ). (mhmedical.com)
  • Researchers from Pfizer Global Research and Development, 23andMe, and the Massachusetts General Hospital have published a study in Nature Genetics, pinpointing 15 genetic loci associated with the risk of developing major depressive disorder (MDD) in individuals of European ancestry. (pharmaceuticalintelligence.com)
  • Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. (pharmaceuticalintelligence.com)
  • Is it, therefore, unrealistic to expect a single gene mutation on a single genetic mouse background to represent a diverse patient population of such a complex disease? (medscape.com)
  • The disease-causing gene is SMN1, and its paralogue, SMN2, is a disease course modifier. (bvsalud.org)
  • The increasing power of GWASs (with the most recently published PD GWAS including 37.7K cases, 18.6K 'proxy-cases' and 1.4M controls, resulting in 90 associated loci 14 ) coupled with the increased availability of cell-specific gene expression data provides a new opportunity to address the potential cellular specificity of disease heritability, as was elegantly demonstrated for schizophrenia in a study by Skene et al. (nature.com)
  • Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) caused by complex gene-environment interactions. (biomedcentral.com)
  • Noteworthy, ATXN1 is the most plausible MS associated gene in the 6p22.3 disease susceptibility locus [ 7 ]. (biomedcentral.com)
  • This growing resource will yield insights into how gene activity influences susceptibility to diseases such as cancer, heart disease, and diabetes. (nih.gov)
  • A new data resource will help establish how differences in an individual's genomic makeup can affect gene activity and contribute to disease. (nih.gov)
  • To help researchers gain deeper insights into how genetic variants affect gene activity and disease susceptibility, NIH launched an effort in 2010 to create a data resource and tissue bank. (nih.gov)
  • This approach can reveal variants that affect gene activity, called expression quantitative trait loci (eQTLs). (nih.gov)
  • The participants suggested approaches to (1) improve reproducibility (e.g., consideration of microbiota, environmental controls, genetic interactions, and genetic diversity), (2) understand innate physiological processes (e.g., molecular factors in disease progression), and (3) enhance translatability for complex diseases (e.g., candidate gene identifications across multiple species). (nih.gov)
  • We will then combine these data with the results from our genetic association studies to allow us to move rapidly from an associated locus to an understanding of the dysregulated gene. (sanger.ac.uk)
  • We identify Nox3 as the associated gene for susceptibility to NIHL that the genetic susceptibility is frequency specific and that it occurs at the level of the cochlear synaptic ribbon. (prolekarniky.cz)
  • The discovery of gene by environment interactions in human disease, such as susceptibility to NIHL, has many inherent difficulties, most notably, controlling for exposure. (prolekarniky.cz)
  • This well-established chromosome 10q24 locus contains leucine-rich, glioma-inactivated 1 ( LGI1 ) gene, which has a putative role in development [ 11 ]. (hindawi.com)
  • Further, EUROSPIN partners developed multiple new mouse lines that allow for the targeted purification and/or imaging of disease relevant gene products as well as new disease models. (europa.eu)
  • Studies on disease-relevant gene products concentrated on a very wide array of proteins. (europa.eu)
  • Finally, EUROSPIN studies on neuronal networks in vitro and in vivo defined new principles of network function in cerebellum and amygdala and led to a first characterization of the role of defined disease gene products in amygdala function and related behavioral outputs. (europa.eu)
  • On aggregate, EUROSPIN work on a large number of disease gene products has yielded a wealth of insights into the mechanism by which the respective mutation or loss of such proteins might cause disease phenotypes. (europa.eu)
  • The role of the PLA2G6 gene in neurodegenerative diseases. (beds.ac.uk)
  • Our work shows that CNVs play an important role in shaping complex traits in healthy populations and that their study can reveal new gene functionalities. (eshg.org)
  • While we found low mtDNAcn in brain regions affected by pathologies, the absence of associations with mtDNA heteroplasmy burden indicates that mtDNA point mutations and small indels are unlikely to be involved in the pathogenesis of late-onset neurodegenerative diseases. (biomedcentral.com)
  • ATXN1 maps to 6p22.3, within the 233 loci associated with an increased risk of developing MS. Toxic gain-of-function mutations in ATXN1 cause the neurodegenerative disorder spinocerebellar ataxia type 1 (SCA1). (biomedcentral.com)
  • It is a progressive neurodegenerative disorder, characterized by the prevalence of extracellular Aβ plaques and intracellular neurofibrillary tangles, derived from the proteolysis of the amyloid precursor protein (APP) and the hyperphosphorylation of microtubule-associated protein tau, respectively. (frontiersin.org)
  • Major Depressive Disorder Loci Discovered in Large GWAS Enabled by 23andMe Participants' Data. (pharmaceuticalintelligence.com)
  • According to the latest clinic diagnosis criteria of MDS (Movement Disorder Association 2015), the diagnosis of PD need to meet the following criteria: rest tremor and bradykinesia in limbs, clinic symptoms of PD are effectively improved by L-dopa, disease duration is usually accompanied by non-motor symptoms especially in early stage, and discrimination from other neural disease [ 3 ]. (biomedcentral.com)
  • Temporal lobe epilepsy (TLE) is usually regarded as a polygenic and complex disorder. (hindawi.com)
  • Alzheimer disease (AD) is a neurodegenerative disorder marked by cognitive and behavioral impairment that significantly interferes with social and occupational functioning. (medscape.com)
  • 7 Considering parkinsonism as just the tip of the iceberg of a multifaceted and complex disorder, PD might be better viewed as a 'centrosympathomyenteric neuronopathy,' as per Langston. (touchneurology.com)
  • Alzheimer Disease (AD) is a neurodegenerative disorder that gradually destroys brain function. (biomedcentral.com)
  • ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. (nih.gov)
  • Furthermore, the identification of risk single nucleotide polymorphisms (SNPs) at the SNCA locus through genome-wide association studies (GWAS) of sporadic PD 9 provides support for the importance of SNCA -related pathways and, by implication, neurons in both sporadic and Mendelian forms of PD. (nature.com)
  • Their findings reinforce pathways previously implicated in Alzheimer s disease pathology, including immune response, inflammation, cell migration and lipid transport pathways. (neurodegenerationresearch.eu)
  • Like their mammalian counterparts, they have complex biochemical pathways, most of which are conserved. (frontiersin.org)
  • Together these findings will highlight key targets and pathways that work inside the HPK-1 controlled longevity program which will provide us with key therapeutic targets which could aid in therapy for age-related diseases. (rochester.edu)
  • Mitochondria are complex multi-functional organelles involved in various pathways including fatty acid and cholesterol synthesis, apoptosis, calcium signaling, and adenosine triphosphate generation [ 1 , 2 ]. (biomedcentral.com)
  • In both cell-autonomous systems and complex organisms, ceramides modify intracellular signaling pathways to slow anabolism, ensuring that catabolism ensues. (jci.org)
  • However, many more causal loci remain to be discovered. (nih.gov)
  • I am fascinated by the unique ability of human genetic variation to provide causal insights into disease biology. (sanger.ac.uk)
  • The goals of my research are thus to use high-throughput screens to gain causal insights into the biological basis of human disease, identify new drug targets and determine the patients who will benefit most from these drugs. (sanger.ac.uk)
  • At that time I was particularly fascinated by neurodegenerative diseases and was drawn to genetics as a means of discovering causal disease biology in an organ as mysterious as the brain. (sanger.ac.uk)
  • 11. Linking protein to phenotype with Mendelian Randomization detects 38 proteins with causal roles in human diseases and traits. (nih.gov)
  • Using WGS-based tools for SMN1/2 genomic region analysis is not only an efficient method in terms of time but will also enable more complex analysis such screening for markers related with a silent carrier status and identification of further genetic modifiers. (bvsalud.org)
  • In addition to the well-established association at the APOE locus, they identified 19 genomic regions significantly associated with late-onset Alzheimer s disease, 11 of which are new susceptibility loci. (neurodegenerationresearch.eu)
  • Carl is a statistical geneticist interested in using genetic and genomic data to further our understanding of common complex diseases. (sanger.ac.uk)
  • In addition, I am excited by the power of high-throughput genetic and genomic screens to discover hitherto unappreciated aspects of disease pathology. (sanger.ac.uk)
  • Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. (nih.gov)
  • Physiology of quantal norepinephrine release from somatodendritic sites of neurons in locus coeruleus. (bio-protocol.org)
  • Hypocretin-1 Potentiates NMDA Receptor-Mediated Somatodendritic Secretion from Locus Ceruleus Neurons. (bio-protocol.org)
  • She was appointed as an associated professor and Ph.D. supervisor at Peking University and Capital Medical University, working on molecular mechanisms of membrane trafficking in neurons and glia and neurodegenerative diseases. (xjtlu.edu.cn)
  • In ageing, the environmental and genetic factors work together and overactive major histocompatibility complex pathway to regulate immune reactions in central nerve system which resulting in neural degeneration, especially in dopaminergic neurons. (biomedcentral.com)
  • Tau-positive neuronal inclusions in neurons of the substantia nigra (no alpha synuclein-positive inclusions, as are found in Parkinson disease). (medscape.com)
  • Although the proteins involved in these diseases are different, they have in common the accumulation of pathological protein inclusions in neurons. (springer.com)
  • Certain subtypes of T cells (CD8+) have been shown to bind to the antigen: MHC class 1 complex on the cell surface promoting further immune responses leading to cell damage and finally death of the neurons. (staycured.com)
  • Of these results however, even the most robust marker for AD susceptibility, the ε4 allele of APOE, is neither necessary nor sufficient for AD diagnosis. (mhmedical.com)
  • thus, the APOE variants do not give a definite prediction of the disease by themselves. (biomedcentral.com)
  • Given its high sporadic incidence, ALS is considered to be a complex disease that is influenced by many environmental triggers and likely many genetic susceptibility and resistance loci. (medscape.com)
  • Late-onset sporadic forms of neurodegenerative diseases are devastating conditions imposing an increasing burden on healthcare systems worldwide. (nature.com)
  • Typically, familial mutation-linked neurodegeneration emerges during the fifth decade of life, whereas the onset of sporadic neurodegenerative disease usually occurs during the seventh decade or even later (Cohen and Dillin 2008 ). (springer.com)
  • Only 5%-10% of PD patients have familial forms of the disease [ 8 ], and PD has traditionally been considered as a largely sporadic disease. (biomedcentral.com)
  • The identification of loci where single nucleotide polymorphisms (SNPs) related to MDD exist could provide better insight into the neurobiology of depression, and therefore better treatment options. (pharmaceuticalintelligence.com)
  • This Request for Applications (RFA), "Methods for Discovering and Scoring Single Nucleotide Polymorphisms", is related to several priority areas, including cancer, heart disease and stroke, diabetes and chronic disability conditions, maternal and infant health, and others. (nih.gov)
  • Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. (nih.gov)
  • Complex human traits that are exclusive of our lineage are the basis of our societies and have huge socio-economic impact. (upf-csic.es)
  • 23andMe, a private biotechnology company situated in California, offers a DNA sequencing service in which consumers send in a saliva swab for testing, and later receive a report listing the findings of the analysis related to ancestry, physical and behavioral traits, along with risk of inheriting certain diseases. (pharmaceuticalintelligence.com)
  • The environment can be carefully controlled, facilitating the study of complex traits like NIHL. (prolekarniky.cz)
  • This xQTL project will provide a rich resource of multi-omics datasets, analysis pipelines, and an xQTL atlas for the research community studying AD/ADRD and other complex neurodegenerative traits. (wustl.edu)
  • 2. Leveraging brain cortex-derived molecular data to elucidate epigenetic and transcriptomic drivers of complex traits and disease. (nih.gov)
  • Currently, my research investigates the role of copy number variants (CNVs) in shaping complex human traits and common diseases. (eshg.org)
  • Chiara will speak about " The impact of copy number variants on complex human traits " in the session C03 Bioinformatics, machine learning and statistical methods . (eshg.org)
  • O-GlcNAc cycling mutants modulate proteotoxicity in Caenorhabditis elegans models of human neurodegenerative diseases. (nih.gov)
  • Risk could be reduced with a better understanding of the biological processes that modulate susceptibility to damaging noise. (prolekarniky.cz)
  • B cell activation plays a central pathogenic role in the chronic, central nervous system autoimmune disease multiple sclerosis (MS) through several, non-mutually exclusive mechanisms that include the production of antibodies and other neurotoxic products, and antigen presentation with consequent propagation of neuroinflammation [ 1 ]. (biomedcentral.com)
  • Nutrition and physical activity for obesity/chronic disease prevention in underserved communities. (unc.edu)
  • Design and testing of innovative clinical and community-based nutrition and physical activity intervention approaches for chronic disease risk reduction in primarily low income and minority populations. (unc.edu)
  • Here, we review the major components of this dynamic process, which involves hemodynamic alterations, inflammation, and endothelial and epithelial cell injury, followed by repair that can be adaptive and restore epithelial integrity or maladaptive, leading to chronic kidney disease. (jci.org)
  • Better understanding of the cellular pathophysiological processes underlying kidney injury and repair will hopefully result in the design of more targeted therapies to prevent the injury, hasten repair, and minimize chronic progressive kidney disease. (jci.org)
  • However, conditions such as cellular stress, metabolic alterations, pathogens, environmental changes, disease-related mutations and aging can influence proteolytic systems (Hipp et al. (springer.com)
  • The EUROSPIN consortium was initiated with the aim of pursuing a multilevel systems biology approach to determine mechanistic relationships between mutations of synaptic proteins and neurological and psychiatric diseases, and to develop new diagnostic tools and therapies. (europa.eu)
  • Under the abnormal inflammation condition, macrophages pathologically diffuse from blood vessels to CNS and transform into microglias contributed to the pathological development of intracranial neural diseases [ 12 ]. (biomedcentral.com)
  • Apart from the age differences, the clinical presentation of EOAD is very similar to the presentation of late-onset AD (LOAD) and many aspects of the disease overlap with normal again in many clinical and pathological aspects. (biomedcentral.com)
  • This research gives an overview of the molecular mechanisms underlying the disease, opening up to a better understanding of the pathophysiology of this disease. (neurodegenerationresearch.eu)
  • Disease Models & Mechanisms , 16(7):1-21. (upf-csic.es)
  • Despite not being able to precisely assess each subject's disease phenotype, scientists can make more rapid headway by collaborating with biotechnology companies in the quest to better understand the biological mechanisms of depression. (pharmaceuticalintelligence.com)
  • Growing evidence indicates that alterations in these major proteolytic mechanisms lead to a demise in proteostasis, contributing to the onset and development of distinct diseases. (springer.com)
  • In this review, we discuss recent findings and open questions on how targeting proteolytic mechanisms could be applied for disease intervention. (springer.com)
  • Protein clearance mechanisms in health and disease. (springer.com)
  • 14. Integrative multiomics analysis highlights immune-cell regulatory mechanisms and shared genetic architecture for 14 immune-associated diseases and cancer outcomes. (nih.gov)
  • Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. (nih.gov)
  • Since then my group have applied GWAS to several immune-mediated diseases, predominantly inflammatory bowel disease (IBD), and identified more than 280 loci associated with disease. (sanger.ac.uk)
  • Decoding the genetic regulation of B cell function is therefore necessary to further our understanding of disease pathogenesis and advance next generation therapies. (biomedcentral.com)
  • Furthermore, scientists are relatively unanimous in their opinion about the role of the dopamine system in the etiology and pathogenesis of the disease. (consortium-psy.com)
  • Motor and cognitive control are associated with noradrenergic innervation of the cortex, arising from the locus coeruleus (LC) noradrenergic system. (nihr.ac.uk)
  • It also potentially improves disease management and quality of life for AD patients, as an earlier diagnosis allows initiation of medication and treatment. (frontiersin.org)
  • Structural and molecular imaging has contributed to a better understanding of the pathophysiology of neurodegenerative dementias and is increasingly being adopted into clinical practice for early and accurate diagnosis. (nihr.ac.uk)
  • Much of current biomedical research, in both the public and private sectors, is based upon the expectation that understanding the genetic contribution to disease will revolutionize diagnosis, treatment, and prevention. (nih.gov)
  • There is no currently available therapy that slows the progression of the underlying disease or adequately relieves the wide range of symptoms in people with more advanced PD. (nih.gov)
  • RESEARCH OBJECTIVES Background Genetic factors appear to contribute to virtually every human disease, conferring susceptibility or resistance, affecting the severity or progression of disease, and interacting with environmental influences. (nih.gov)
  • Undoubtedly, genetic factors play an important role in susceptibility and resistance to COVID-19. (bvsalud.org)
  • AD is a heterogeneous, multifactorial disease, and the challenge in AD research is to fully understand how the multiple etiologies and prodromal processes contribute to the pathophysiology of AD. (nih.gov)
  • Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types. (nature.com)
  • PD disease processes begin well before people start exhibiting motor symptoms. (nih.gov)
  • I am a co-PI of the IBD bioresource , a collection of more than 30K IBD patients consented for recall by phenotype and genotype, and The Health Data Research Hub for Inflammatory Bowel Disease which collates and processes routine clinical data for these patients to make it more accessible for research. (sanger.ac.uk)
  • 4. Identifying drug targets for neurological and psychiatric disease via genetics and the brain transcriptome. (nih.gov)
  • I moved to Oxford at the beginning of 2007 to work on the inflammatory bowel disease arm of the WTCCC, buoyed by the fact that even linkage analysis managed to map a risk locus for IBD ( NOD2 ). (sanger.ac.uk)
  • First-degree relatives of patients with AD have a 20% to 44% lifetime risk for the disease. (mhmedical.com)
  • The team then created a weighted genetic risk score (GRS) in which they compared the 17 SNPs with factors including medication use, comorbid diseases and behavioral phenotypes, all of which were correlated with the GRS. (pharmaceuticalintelligence.com)
  • Excess sedentary time (ST) is recognized as an important modifiable risk factor for coronary heart disease (CHD). (nihr.ac.uk)
  • Method: The investigators of the FunGen-AD consortium are using multiple approaches, including brain single cell data acquisition, human stem cell modeling and high through put CRISPR-based screens, to understand how AD variants lead to changes across molecular networks, and understand how specific risk variants affect disease in diverse populations. (wustl.edu)
  • 15. Inferring the genetic relationship between brain imaging-derived phenotypes and risk of complex diseases by Mendelian randomization and genome-wide colocalization. (nih.gov)
  • There is no effective cure for LOAD, leaving the treatment efforts to depend on preventive cognitive therapies, which stand to benefit from the timely estimation of the risk of developing the disease. (biomedcentral.com)
  • To apply these preventive treatments, a key component is detecting those individuals at risk at an early stage of the disease. (biomedcentral.com)
  • Out of 15,489,173 SNPs, we identified 18,191 significant SNPs for severe and 11,799 SNPs for resistant phenotype, showing that a great number of loci were significant in different COVID-19 representations. (bvsalud.org)
  • After the joint analysis, 17 SNPs were identified at 15 different loci. (pharmaceuticalintelligence.com)
  • The availability of a dense collection of SNPs will stimulate many areas of biological research, including the identification of the genetic components of disease. (nih.gov)
  • Today, advances in next-generation sequencing technologies and massive reductions in sequencing costs have generated a wealth of data that are revealing the genetic basis for many human neurodegenerative diseases. (medscape.com)
  • In the long term, advances in these areas will enhance our ability to investigate, diagnose and ameliorate human disease with a significant epigenetic component. (nih.gov)
  • New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. (nih.gov)
  • The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure-disease relationships and the interaction of genetic and environmental factors in disease occurrence. (nih.gov)
  • Scientists have only just begun to understand how these variations in different tissues of the body affect human biology and disease. (nih.gov)
  • As the GTEx project continues to collect and analyze tissue samples, this growing resource will help reveal how genetic variation affects human biology and suggest new approaches to disease. (nih.gov)
  • The importance of the stem cell epigenome to maintaining pluripotency and regulating cell differentiation, and the demonstrated susceptibility to chemical modulation, makes human embryonic stem (hES) cells an ideal in vitro model system for testing chemicals for epigenotoxic potential, and are especially relevant as a model for developmental toxicity. (nih.gov)
  • Synaptotagmins: links to human disease. (xjtlu.edu.cn)
  • I became interested in human disease genetics during my time as a biomedical sciences undergraduate at the University of Sheffield, UK. (sanger.ac.uk)
  • Interrogating these patterns of genome diversity we can infer what are the forces that affect living organisms, how and when they act and how do they affect such various things as biodiversity, human emotions or the differential susceptibility of different persons to certain diseases. (upf-csic.es)
  • We study world-wide patterns of disease susceptibility distribution to ascertain how these may have been influenced by recent human evolution. (upf-csic.es)
  • The findings come from an international research team led by Michael Ewers, Institute for Stroke and Dementia Research, Ludwig-Maximilians-Universität München, Germany, and Christian Haass, Ludwig-Maximilians-Universität München, Germany and German Center for Neurodegenerative Diseases. (nih.gov)
  • However, whether the associations of genetic susceptibility with CHD incidence can be modified by replacing wearable-device-measured ST with physical activity (PA) is unknown. (nihr.ac.uk)
  • 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)
  • Here we will discuss the specificity of various NF-κB proteins, their role in inflammatory disease, the regulation of NF-κB activity by IκB proteins and IκB kinase (IKK), and the development of therapeutic strategies aimed at inhibition of NF-κB. (jci.org)
  • 1 , 2 Existing symptomatic treatments do not alter the course of the disease and their effectiveness declines with time, which makes the identification of potential therapeutic targets of key importance. (nature.com)
  • While continuing her endeavor in mechanistic studies, her current research focuses on identification of potential drug targets and novel therapeutic interventions in neurodegenerative diseases. (xjtlu.edu.cn)
  • Mice offer numerous benefits (e.g., size, cost, genetic similarity with humans) but present significant challenges (e.g., rigor and reproducibility, modeling for complex diseases, incorporation of genetic diversity) for investigators. (nih.gov)
  • By including gnotobiotic mouse models of inflammatory bowel disease, in addition to wild type mice, Dr. Bhatt is executing granular and mechanistic studies of host-microbiota interactions, and how they impact gastrointestinal health. (unc.edu)
  • In this manuscript, we describe, for the first time, an association analysis with correction for population structure for the mapping of several loci for susceptibility to NIHL in inbred strains of mice. (prolekarniky.cz)
  • The genetic basis of NIHL has been clearly demonstrated in animals as different susceptibilities to noise have been seen in different inbred stains of mice [ 4 ]. (prolekarniky.cz)
  • Mutant huntingtin led to abnormally long primary cilia and disorganized cilia layers in mice and humans with Huntington disease. (jci.org)
  • Transforming technologies are needed to enable researchers to discover and monitor epigenetic events, changes, and alterations related to development and disease. (nih.gov)
  • Current research efforts are focused on understanding how alterations in proteolytic systems can contribute to the onset and prognosis of disease with the aim to identify novel therapeutic approaches (Wang et al. (springer.com)
  • The mouse has been an essential animal model for studies in hearing loss, and advances in mouse genetics, including genome sequence and high density single-nucleotide polymorphism (SNP) maps, provide a suitable system for the study of a complex trait such as NIHL [ 6 ]. (prolekarniky.cz)
  • Disruption of this complex regulatory circuit by exposure to environmental agents and/or pharmaceuticals during embryogenesis can lead to spontaneous abortions and birth defects, as well as adverse health and cognitive effects later in life. (nih.gov)
  • Progressive supranuclear palsy (PSP) is a neurodegenerative syndrome that is clinically characterized by progressive postural instability, supranuclear gaze palsy, parkinsonism and cognitive decline. (e-jmd.org)
  • Changes in the mitochondrial DNA copy number (mtDNAcn) and increased mitochondrial DNA mutation burden have both been associated with neurodegenerative diseases and cognitive decline. (biomedcentral.com)
  • Mitochondrial content and mtDNAcn independently explained variance in cognitive function unaccounted by pathologies, implicating complex mitochondrial recalibrations in cognitive decline. (biomedcentral.com)
  • It is well established, for example, that cognitive impairments often follow conditions of metal imbalance, which can be either deficiency, as in Menkes' disease, or accumulation, as in Wilson's disease or aceruloplasminemia [ 1 - 6 ]. (hindawi.com)
  • This finding may lead to insights into why certain diseases affect men and women differently. (nih.gov)
  • The administration of B cell depleting antibodies to people with MS has made a major impact on the management of the disease, definitely confirming their role in the expression, perhaps also initiation of the autoimmune response [ 2 ]. (biomedcentral.com)
  • 2014 ). Loss of proteostasis is a hallmark of aging, further strengthening a role of proteolytic deficits in the onset of neurodegenerative diseases (Lopez-Otin et al. (springer.com)
  • There is growing evidence, however, that inflammation might play a causative role in PD rather than being a consequence or an epiphenomenon of the neurodegenerative process. (staycured.com)
  • 16. A data-driven approach for studying the role of body mass in multiple diseases: a phenome-wide registry-based case-control study in the UK Biobank. (nih.gov)
  • Molecular basis of unique specificity and regulation of group VIA calcium-independent phospholipase A(2) (PNPLA9) and its role in neurodegenerative diseases. (beds.ac.uk)
  • Although the existing literature on the etiology of the disease is diverse and contradictory, the role of the hereditary nature of schizophrenia is the most proven. (consortium-psy.com)
  • For example, some ALS patients can progress very rapidly in their disease, while others experience only weakness for more extended periods of time. (medscape.com)
  • [ 4 , 25 ] In addition to variation in the age of onset, ALS patients may present with either bulbar or limb onset, and may even exhibit tremendous variation in the sequence of limbs affected and how the disease progresses. (medscape.com)
  • The ability to assess the neurological state of patients with neurodegenerative diseases on a continuous basis is an important component of future care for these chronically ill patients. (researchgate.net)
  • 2014 ). In addition, patients with inflammatory and infectious diseases as well as cancer also present changes in proteolytic systems (Dang et al. (springer.com)
  • The work of EUROSPIN led to the establishment of a large protein-protein-interaction (PPI) database, which was complemented with systematic data on high-throughput electrophysiological analyses and on behavioral phenotypes of disease-relevant mouse models, as well as with data on dozens of new antibodies generated by EUROSPIN (eurospindb.genes2cognition.org). (europa.eu)
  • 3. Mendelian randomization and genetic colocalization infer the effects of the multi-tissue proteome on 211 complex disease-related phenotypes. (nih.gov)
  • Many neurological diseases present with tremendous clinical heterogeneity. (medscape.com)