• Huntington's disease (HD) is a severe autosomal-dominant neurodegenerative disorder caused by a mutation within a gene, encoding huntingtin protein. (frontiersin.org)
  • Huntington's disease (HD) is a severe neurodegenerative pathology characterized by motor dysfunction, cognitive decline and the presence of mental disorders. (frontiersin.org)
  • Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. (nature.com)
  • Monogenic gain-of-function protein aggregation diseases, including Huntington's disease, exhibit substantial variability in age of onset, penetrance, and clinical symptoms, even between individuals with similar or identical mutations. (biomedcentral.com)
  • Objective: Polyglutamine proteins can cause a wide range of neurodegenerative disorders upon long-range expansions such as Huntington's disease and spinocerebellar ataxia (SCA). (videolectures.net)
  • Scientists have created a tool for mopping up the clumps of mutant protein that drive neurodegeneration in Huntington's disease. (scienceblog.com)
  • The striatum is the part of the brain most affected by Huntington's disease. (scienceblog.com)
  • A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. (nature.com)
  • Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. (nature.com)
  • Inactivation of the mouse Huntington's disease gene homolog hdh . (nature.com)
  • Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. (nature.com)
  • Trottier, Y., Biancalana, V. & Mandel, J.L. Instability of CAG repeats in Huntington's disease: relation to parental transmission and age of onset. (nature.com)
  • Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation. (nature.com)
  • Huntington's disease (HD) is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain. (hdsa.org)
  • Since 1999, the Huntington's Disease Society of America has committed more than $20 million to fund research, with the goal of finding effective treatments to slow Huntington's disease. (hdsa.org)
  • Today we continue her legacy by bringing together the entire community to provide help and hope to all families affected by Huntington's disease. (hdsa.org)
  • Huntington's disease affects a part of the brain called the striatum that we know is very important for controlling behavior. (hdsa.org)
  • The goal of our research is to develop a novel eye-movement technique to aid the diagnosis and progression monitoring of Huntington's disease (HD). (hdsa.org)
  • While much study has been devoted to genetic "triggers" of CNS neurodegeneration-notably mutant Htt in Huntington's disease (HD)-such inherited triggers are typically expressed from early fetal development and are fundamentally inaccessible to timely clinical intervention. (hdsa.org)
  • Researchers have shown that the core of the protein clumps found in the brains of people with Huntington's disease have a distinctive structure, a finding that could shed light on the molecular mechanisms underlying the neurodegenerative disorder. (neurodegenerationresearch.eu)
  • In Huntington's and several other progressive brain diseases, certain proteins aggregate to form plaques or deposits in the brain, said senior investigator Patrick C.A. van der Wel, Ph.D., assistant professor of structural biology at Pitt School of Medicine. (neurodegenerationresearch.eu)
  • The gene associated with Huntington's makes a protein that has a repetitive sequence called polyglutamine. (neurodegenerationresearch.eu)
  • He added Huntington's is one of many neurodegenerative diseases in which unusual protein deposition occurs in the brain, suggesting similar biochemical mechanisms may be involved. (neurodegenerationresearch.eu)
  • Background: Huntington's disease (HD) is the most common polyglutamine neurodegenerative disorder. (lu.se)
  • Normal Htt shows a common alpha-helical structure but conformational changes in the form with beta strands are the principal cause of Huntington's disease. (benthamscience.com)
  • Huntington's disease is a genetic neurological disorder caused by a repeated expansion of the CAG trinucleotide, causing instability in the N-terminal of the gene coding for the Huntingtin protein. (benthamscience.com)
  • Mutant Huntingtin is the cause of the complex neurological metabolic alteration of Huntington's disease, resulting in both the loss of all the functions of normal Huntingtin and the genesis of abnormal interactions due to the presence of this mutation. (benthamscience.com)
  • In this episode of AudioHelicase, Whitehead Institute Member Ankur Jain discusses how RNA can clump in cells and the diseases, such as Huntington's and amyotrophic lateral sclerosis (ALS), that are associated with these aggregations. (mit.edu)
  • These are the sequences associated with certain neurodegenerative diseases, such as Huntington's disease, or amyotrophic lateral sclerosis. (mit.edu)
  • Perhaps a better-known example is Huntington's disease, where there's a stretch the sequence CAG, which gets copied too many times in the Huntington gene. (mit.edu)
  • Golgi apparatus and Huntington's Disease" Encyclopedia , https://encyclopedia.pub/entry/14805 (accessed December 08, 2023). (encyclopedia.pub)
  • Huntington's disease (HD) is caused by expansion of polyglutamine repeats in the protein huntingtin, which affects the corpus striatum of the brain. (encyclopedia.pub)
  • Polyglutamine diseases, including Huntington's disease, arise from multiple repeats of the glutamine codon-for example CAGCAGCAGCAG-in a variety of genes. (nih.gov)
  • These observations correlate with the neuronal death observed in conditions such as Huntington's disease. (nih.gov)
  • In individuals with Huntington's disease (HD), sleep disturbances constitute an additional burden that may exacerbate disease outcomes and impact patients' quality of life. (iospress.com)
  • This special issue of the Journal of Huntington's Disease (JHD) reviews what is, and perhaps more importantly, what is not known about sleep and circadian rhythms in HD. (iospress.com)
  • In " Sleep Disorders and Circadian Disruption in Huntington's Disease ," Sandra Saade-Lemus, MD, and Aleksandar Videnovic, MD, both of the Department of Neurology, Massachusetts General Hospital, Harvard Medical School, point out that despite evidence of sleep and circadian abnormalities, sleep alterations are underreported by patients and underrecognized by health professionals. (iospress.com)
  • Rats transgenic for Huntington's disease (tgHD51 CAG rats), surviving up to two years, represent an animal model of HD similar to the late-onset form of human disease. (hindawi.com)
  • Huntington's disease (HD) is an autosomal dominant inherited disorder belonging to the group of systemic brain atrophies. (hindawi.com)
  • The abnormal amplification of a CAG repeat in the gene coding for huntingtin (HTT) leads to Huntington's disease (HD). (uni-muenchen.de)
  • University of Bristol scientists have discovered a novel pathology occurring in several human neurodegenerative diseases including Huntington's disease. (integratedhlth.co.uk)
  • An article published in the Brain Pathology journal describes how SAFB1 expression occurs in both spinocerebellar ataxias and Huntington's disease. (integratedhlth.co.uk)
  • The researchers analysed SAFB1 expression in the post-mortem brain tissue of spinocerebellar ataxias (SCA's), Huntington's disease (HD), Multiple sclerosis (MS), Parkinson's disease patients and controls. (integratedhlth.co.uk)
  • Here, we studied the impact of IGF2 signaling on protein aggregation in models of Huntington's disease (HD) as proof of concept. (uchile.cl)
  • His current research work involve systems biology of Huntington's disease, chromosome instability, non-coding RNAs in cancers, and cancer drug resistance mechanisms. (kgi.edu)
  • Huntingtin is a disease gene linked to Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons. (thermofisher.com)
  • The genetic defect leading to Huntington's disease may not necessarily eliminate transcription, but may confer a new property on the mRNA or alter the function of the protein. (thermofisher.com)
  • The protein encoded by the ATXN3 gene contains CAG repeats in the coding region, and the expansion of these repeats from the normal 13-36 to 68-79 is the cause of Machado-Joseph disease. (wikipedia.org)
  • In most people, the number of CAG repeats in the ATN1 gene ranges from 6 to 35. (medlineplus.gov)
  • At the molecular level, HD occurs due to an increase in the number of CAG repeats in the first exon of the gene encoding the huntingtin protein. (frontiersin.org)
  • The age of onset of the disease varies inversely with the number of CAG repeats. (jci.org)
  • Individuals with juvenile onset usually have over 55 repeats, and they usually inherit the gene from their father. (jci.org)
  • The most common SCA are characterized by expanded CAG trinucleotide that repeats the encode glutamine amino acid, the so-called polyglutamine diseases. (scielo.br)
  • Disease-causing mutations involve a lengthening of part of the gene for huntingtin, so that it repeats three letters (CAG) of the genetic code dozens of times. (scienceblog.com)
  • The mutation consists of an unstable expansion of CAG repeats within the coding region of the HD gene, which expresses the protein huntingtin. (lu.se)
  • He also noted that such repeats are found in the disease genes associated with certain neurodegenerative disorders. (mit.edu)
  • And virtually all of these diseases have this peculiar characteristic that short repeats do not result in disease onset. (mit.edu)
  • But only when the number of repeats exceeds a certain critical threshold that results in disease manifestation. (mit.edu)
  • How exactly these repeats are resulting in the disease is not known. (mit.edu)
  • What we know so far is that long repeats result in a disease, short repeats to not. (mit.edu)
  • There's another feature that the more the number of repeats, the sooner the disease hits. (mit.edu)
  • For instance, an individual carrying 50 repeats will likely get Huntington disease symptoms earlier than the individual carrying 45 repeats or 40 repeats only. (mit.edu)
  • And again, it has remained mysterious why there is this anticorrelation between the number of repeats and the age of disease onset. (mit.edu)
  • The polyglutamine repeats in mutant huntingtin cause its aggregation and elicit toxicity by affecting several cellular processes, which include dysregulated organellar stress responses. (encyclopedia.pub)
  • it results from expansion of polyglutamine repeats in the protein huntingtin [ 1 ] . (encyclopedia.pub)
  • Since these diseases likely share similar mechanisms, a better understanding of how these repeats cause dysfunction could aid in the development of therapies. (nih.gov)
  • Lately, in 1993, gene IT15 (interesting transcript 15), which codes unstable protein huntingtin (htt) comprising variable number of CAG repeats, was identified [ 5 ]. (hindawi.com)
  • Specifically, it occurs in the CAG repeats of the gene, which consists of a cytosine-adenine-guanine repetitive DNA sequence that codes for a polyglutamine amino acid sequence, with glutamine being the corresponding amino acid for these triplet bases. (essex.ac.uk)
  • The more CAG repeats, the earlier the onset of disease and the more severe its expression (phenotype). (msdmanuals.com)
  • A transcriptional co-repressor is a protein that interacts with other DNA-binding proteins to suppress the activity of certain genes, although it cannot attach (bind) to DNA by itself. (medlineplus.gov)
  • The extended CAG region changes the structure of atrophin 1 and how the protein interacts with other proteins to control gene function. (medlineplus.gov)
  • SCA2 is seen as a an increase of dangerous function for the polyglutamine extended ATXN2 proteins. (woofahs.com)
  • In the 1990s, it was discovered that the patients have mutated proteins in which this sequence is too long, yet it has remained unclear how exactly this unusual mutation causes the protein to misbehave, clump together and cause the disease. (neurodegenerationresearch.eu)
  • Scientific and social factors have resulted in a focus on well-studied proteins, leading to a concern that poorly understood genes are unjustifiably neglected. (biorxiv.org)
  • The advent of genome sequencing revealed in humans and other species thousands of genes encoding proteins that had not been identified by previous biochemical or genetic studies. (biorxiv.org)
  • The mystery and the potential biological significance of these unknown genes is enhanced by many of them being well conserved, and many of them being completely unrelated to known proteins and thus lacking clues to their function. (biorxiv.org)
  • When translated into protein the CAG repeat encodes for a polyglutamine stretch in the disease-causing proteins. (biologie-uni-siegen.de)
  • IRP researchers led by Kenneth Fischbeck, M.D. , found that the expanded polyglutamine proteins may act as sticky glue, blocking up their normal clearance process. (nih.gov)
  • It is similar in structure to other proteins associated with neurodegenerative diseases of age. (integratedhlth.co.uk)
  • Huntington disease can be a neurodegenerative disorder due to the polyglutamine do it again in AZD5438 the N terminus from the huntingtin proteins (37). (cancer-ecosystem.com)
  • Ubiquitin-proteasome system (UPS) and autophagy are two major cellular degradation machineries in eukaryotes, both of which are crucial in eliminating misfolded/unfolded proteins to maintain cell and tissue homeostasis and to prevent aging-related changes and a plethora of human diseases. (biomedcentral.com)
  • Together, the discovery of two proteins that can reverse 6meA modifications from mRNA draws attention to the potential regulatory functions of reversible RNA methylation and the role of 6meA in disease. (cmbn.no)
  • This disorder is thus a trinucleotide repeat disorder type I known as a polyglutamine (PolyQ) disease. (wikipedia.org)
  • Frequency and distribution of polyQ disease intermediate-length repeat alleles in healthy Italian population. (nih.gov)
  • For example in HD, the age of neurological onset is strongly associated with the length of polyglutamine (polyQ) expansion in huntingtin protein. (biomedcentral.com)
  • Spinal and bulbar muscular atrophy (SBMA) is caused by the polyglutamine androgen receptor (polyQ-AR), a protein expressed by both lower motor neurons and skeletal muscle. (nih.gov)
  • Suppression of polyQ-AR in the periphery rescued deficits in muscle weight, fiber size, and grip strength, reversed changes in muscle gene expression, and extended the lifespan of mutant males. (nih.gov)
  • The mutation leads to the abnormal expansion of the production of the polyglutamine tract (polyQ) resulting in the form of an unstable Huntingtin protein commonly referred to as mutant Huntingtin. (benthamscience.com)
  • At the protein level, this translates into the expansion of a polyglutamine (polyQ) stretch located at the HTT N terminus, which renders HTT aggregation prone by unknown mechanisms. (uni-muenchen.de)
  • Li says finding an antibody that prefers to bind mutant, aggregated protein could also prove useful in the study of other neurodegenerative disorders, such as Alzheimer's disease or Creutzfeldt-Jakob disease. (scienceblog.com)
  • Dr. Paulson is the Lucile Groff Professor of Neurology for Alzheimer's Disease and Related Disorders in the Department of Neurology. (taubmaninstitute.org)
  • He joined the University of Michigan faculty in 2007, and he currently directs the Michigan Alzheimer's Disease Center and co-directs the University of Michigan Protein Folding Diseases Initiative. (taubmaninstitute.org)
  • Dr. Paulson's research and clinical interests concern the causes and treatment of age-related neurodegenerative diseases, with an emphasis on polyglutamine diseases, Alzheimer's disease and frontotemporal dementia. (taubmaninstitute.org)
  • One of the problems arising from the misfolded Huntingtin is the increase in oxidative stress, which is common in many neurological diseases such as Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis and Creutzfeldt-Jakob disease. (benthamscience.com)
  • Professor Uney said there was scope in the future to broaden the study to include other diseases, such as Alzheimer's, disease. (integratedhlth.co.uk)
  • At the present moment, Alzheimer's disease, other dementias, polyglutamine diseases, and developmental disorders related to PQBP1 are the main targets of our laboratory. (tmd.ac.jp)
  • For more than 15 years, we have been focusing on the proteome and transcriptome analyses of cellular and animal models of Alzheimer's disease, FTLD, polyglutamine diseases and so on, and have obtained novel molecules that are critically involved in the pathomechanisms. (tmd.ac.jp)
  • Especially, we proposed 'DNA damage repair impairment' as a common pathology across multiple neurodegenerative diseasese, and proposed 'intracellular amyloid hypothesis' and 'ultra-early phase pathology hypothesis' as new concepts that might replace previous 'amyloid hypothesis' and provide a new orientation to develop radical therapy against Alzheimer's disease. (tmd.ac.jp)
  • Prof. Okazawa joined a discussion about the latest research topics in Alzheimer's disease (AD) pathology in Alzforum ( link ), in which Prof. Okazawa discussed with the authors about the relationship between three models of ultra-early stage AD pathologies before amyloid plaque formation, TRIAD, PANTHOS and PAAS. (tmd.ac.jp)
  • Prof. Okazawa gave an invited lecture at the 51st annual meeting of the Japanese society for immunology on innate immune function in neurodegenerative diseases such as Alzheimer's disease ( program ). (tmd.ac.jp)
  • HD and Alzheimer's also have similar mechanisms of disease, meaning that a better understanding of HD's pathology could potentially lead to advancements in the research of Alzheimer's and other dementia-causing disorders with similar mechanisms. (essex.ac.uk)
  • Disease onset usually occurs in individuals between the third and fifth decade of life with great variability of clinical presentations 3 3. (scielo.br)
  • In order to identify genes that may modify disease onset and progression, genome-wide association and gene expression studies have been performed 12 , 13 . (nature.com)
  • Although these mutations themselves are causative, many disease characteristics such as age of onset, penetrance, and severity of specific symptoms can vary widely between individuals. (biomedcentral.com)
  • Yet age of onset can vary by several decades in people carrying the same length polyglutamine expansion, and a large proportion of this residual variation is genetic in nature and may be due to polymorphisms in other genes [ 12 - 15 ]. (biomedcentral.com)
  • The serum level of creatinine starts to decrease before the onset of muscle weakness, followed by the emergence of hand tremor, a prodromal sign of the disease. (kennedysdisease.org)
  • That results in the disease onset. (mit.edu)
  • The disease is always fatal with an average survival of 10-15 years after the onset of the first symptoms. (hindawi.com)
  • HD is a mid-life onset autosomal dominant neurodegenerative disease that is characterized by psychiatric disorders, dementia, and involuntary movements (chorea), leading to death in 10-20 years.The huntingtin locus is large, spanning 180 kb and consisting of 67 exons. (thermofisher.com)
  • Huntington disease (HD) is an incurable, adult-onset, autosomal dominant inherited disorder associated with cell loss within a specific subset of neurons in the basal ganglia and cortex. (medscape.com)
  • Voxel-based morphometry revealed grey-matter and white-matter atrophy, even in subjects furthest from predicted disease onset. (medscape.com)
  • However, comparing the HD76 neurons with the previously described low-repeat HD models, we have demonstrated that the severity of calcium signaling alterations does not depend on the length of the polyglutamine tract of the mutant huntingtin. (frontiersin.org)
  • Intermediate length of the polyglutamine coding CAG/CAA trinucleotide repeat in the ATXN2 gene was shown to be a risk factor for amyotrophic lateral sclerosis (ALS). (videolectures.net)
  • HD is an autosomal-dominant hereditary neurodegenerative condition, characterized by a triad of motor, cognitive, and psychiatric features resulting from a polyglutamine expansion mutation in exon 1 of the huntingtin gene. (iospress.com)
  • The discovery of a causative gene mutation (abnormal expansion of the CAG repeat in DRPLA gene) triggered the development of novel neuropathology in DRPLA, which has suggested that Selleck CB-839 polyglutamine-related pathogenesis involves a wide range of central nervous system regions far beyond the systems previously reported to be affected. (dehydrogenase-signal.com)
  • HD is autosomal-dominant, meaning it is caused by a mutation in a non-sex chromosome gene that has a 50% chance of being passed on if one parent has the mutated gene. (essex.ac.uk)
  • The mutation is in the HTT gene that codes for the protein huntingtin (Figure 1). (essex.ac.uk)
  • Huntington disease results from a mutation in the huntingtin ( HTT ) gene (on chromosome 4), causing abnormal repetition of the DNA sequence CAG, which codes for the amino acid glutamine. (msdmanuals.com)
  • Although viewed as a motor neuronopathy, data from patients and mouse models suggest that muscle contributes to disease pathogenesis. (nih.gov)
  • We believe that these findings bear a number of important implications for disease pathogenesis. (neurodegenerationresearch.eu)
  • Androgen-dependent nuclear accumulation of the polyglutamine-expanded AR is an essential step in the pathogenesis, providing therapeutic opportunities via hormonal manipulation and gene silencing with antisense oligonucleotides. (kennedysdisease.org)
  • It remains unknown if sleep disorders precede pathogenesis (and thus represent a risk factor for the disease) or whether they only appear as a debilitating symptom of the pathophysiological alterations. (iospress.com)
  • We provide a new candidate mechanism for modulating the pathogenesis of neurodegenerative diseases sensitive to protein dosage. (nih.gov)
  • Since neurodegenerative disorders are one of the most acute and socially significant problems facing modern medicine, adequate models for these diseases are highly demanded. (frontiersin.org)
  • Clinically, the disease is characterized by complex and variable symptoms that include movement disorders, psychiatric problems and cognitive decline 2 . (nature.com)
  • Andrew, S.E., Goldberg, Y.P. & Hayden, M.R. Rethinking genotype and phenotype correlations in polyglutamine expansion disorders. (nature.com)
  • Nationally, he has directed a national consortium of scientists and physicians studying genetic forms of ataxia, has served on the scientific advisory boards of numerous disease-related national organizations, and is a past chair of the Board of Scientific Counselors at the National Institute for Neurological Disorders and Stroke (NINDS) at the National Institutes of Health. (taubmaninstitute.org)
  • In 2020, he received the Movement Disorders Research Award from the American Academy of Neurology for his pioneering work into the causes and treatment of nucleotide repeat expansion diseases. (taubmaninstitute.org)
  • Researchers have discovered the mechanics of how dopamine transports into and out of brain cells, a finding that could someday lead to more effective treatment of drug addictions and neurological disorders such as Parkinson's disease. (neurodegenerationresearch.eu)
  • Genetic screening for Huntington disease phenocopies in Sweden: A tertiary center case series focused on short tandem repeat (STR) disorders. (cdc.gov)
  • The so-called CAG repeat diseases are characterized by symptoms such as the progressive loss of cognitive abilities and progressive movement disorders. (biologie-uni-siegen.de)
  • There are about 30 known diseases in this family collectively called the repeat expansion disorders. (mit.edu)
  • The goals of our department are to understand the mechanisms underlying neurodegenerative diseases and to develop effective therapeutics for such intractable disorders. (tmd.ac.jp)
  • What's new concerning Parkinson's disease and other movement disorders? (medscape.com)
  • WeMove produced these summaries on the basis of the data presented at the 8th International Congress of Parkinson's Disease and Movement Disorders, held in Rome, Italy, June 14-17, 2004. (medscape.com)
  • Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a debilitating neuromuscular disease characterized by progressive muscular weakness and neuronal degeneration, affecting 1-2 individuals per 100,000 globally. (preprints.org)
  • Machado-Joseph disease, also known as spinocerebellar ataxia-3, is an autosomal dominant neurologic disorder. (wikipedia.org)
  • Spinocerebellar ataxia type 2 (SCA2) is really a dominantly inherited uncommon polyglutamine disease the effect of a CAG do it again expansion within the ataxin-2 (do it again is closely linked with disease starting point and intensity. (woofahs.com)
  • Moreover, USP7 knockdown suppressed disease phenotypes in SBMA and spinocerebellar ataxia type 3 (SCA3) fly models, and monoallelic knockout of Usp7 ameliorated several motor deficiencies in transgenic SBMA mice. (kennedysdisease.org)
  • Spinocerebellar ataxia type 3 (SCA3) is a genetic degeneration disease of the nervous system with ataxia as the main clinical manifestation, and the most frequent subtype of SCA3 is known to be caused by CAG repeat expansions of more than 55 units in ATXN3. (bvsalud.org)
  • Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). (bvsalud.org)
  • The potential value of disease-modifying therapy in patients with spinocerebellar ataxia type 1: an early health economic modeling study. (cdc.gov)
  • We were also able to demonstrate how SAFB1 binds the SCA1 gene with the disease causing polyglutamine expansion (which causes spinocerebellar ataxia 1). (integratedhlth.co.uk)
  • [ 7 ] More recent data from striatal neuronal cultures transfected with mutant huntingtin and transgenic mice carrying the spinocerebellar ataxia-1 (SCA-1) gene (another CAG repeat disorder) suggest that NIIs may not be necessary or sufficient to cause neuronal cell death, but translocation into the nucleus is sufficient to cause neuronal cell death. (medscape.com)
  • The main objective of the research was to examine the consequences of mutant ATXN2 on genome-wide appearance of spinal-cord (SC) genes and integrate adjustments into a construction of previously defined transcriptomic adjustments in ALS versions. (woofahs.com)
  • Cell culture studies revealed that IGF2 treatment decreases the load of intracellular aggregates of mutant huntingtin and a polyglutamine peptide. (uchile.cl)
  • Administration of IGF2 into the brain of HD mice using gene therapy led to a significant decrease in the levels of mutant huntingtin in three different animal models. (uchile.cl)
  • TRACK-HD is a prospective observational study that reported 12-month longitudinal changes in 116 pre-manifest individuals carrying the mutant Huntington gene (preHD), 114 patients with early HD, and 115 age- and sex-matched controls. (medscape.com)
  • One region of the ATN1 gene contains a particular DNA segment known as a CAG trinucleotide repeat. (medlineplus.gov)
  • DRPLA results from an increased number of copies (expansion) of the CAG trinucleotide repeat in the ATN1 gene. (medlineplus.gov)
  • This is thought to be caused by an expanded, unstable trinucleotide repeat in the huntingtin gene, which translates as a polyglutamine repeat in the protein product. (thermofisher.com)
  • Several neurodegenerative diseases appear to involve defects in protein folding and metabolism, leading to the accumulation of protein aggregates inside cells," he says. (scienceblog.com)
  • Our study suggests a strategy for dissecting the harmful effects of these protein aggregates in other diseases. (scienceblog.com)
  • In 1997, his lab described abnormal protein aggregates in the polyglutamine diseases, which now are recognized as a pathological hallmark in this important class of inherited diseases. (taubmaninstitute.org)
  • Lessons learned in this disease could help foster understanding of how these types of diseases develop, and what role the protein aggregates play. (neurodegenerationresearch.eu)
  • In Parkinson's disease, the protein alpha-synuclein aggregates within neurons of patients and appears to propagate across interconnected areas of the brain. (neurodegenerationresearch.eu)
  • I'm Lisa Girard, director of communications at Whitehead Institute, and in this episode, I'll be talking with Ankur about RNA aggregates and what they might mean for our understanding of certain neurodegenerative diseases. (mit.edu)
  • [ 2 ] All dementia share common molecular mechanisms responsible for disease etiology and progression, such as hypoxia and oxidative stress, neuroinflammation, mitochondrial bioenergetics, neurodegeneration, and blood-brain barrier permeability. (medscape.com)
  • Roles spastic paraplegia genes in organisation of axonal endoplasmic reticulum: Relevance of a forgotten compartment to neurodegeneration? (edu.hk)
  • We previously reported that targeting the transcription factor XBP1, a key mediator of the ER stress response, delays disease progression and reduces protein aggregation in various models of neurodegeneration. (uchile.cl)
  • [ 5 ] This was later characterized as an expanded tandem (cytosine-adenine-guanine [CAG]) repeat in the first exon of the androgen receptor gene. (medscape.com)
  • The disease is caused by a pathogenic expansion of polyglutamine residues in the androgen receptor protein, which acts as a key transcriptional regulator for numerous genes. (preprints.org)
  • This gene encodes a nuclear polyglutamine-binding protein that is involved with transcription activation. (nih.gov)
  • As with many neurodegenerative diseases, both rare autosomal-dominant forms of AD and more common sporadic forms with genetic risk factors without causative mutations exist. (medscape.com)
  • Resistance to protein aggregation and the ability to restrict its associated cellular dysfunction are independently controlled by the natural variation in genetic background, revealing important new considerations in the search for targets for therapeutic intervention in conformational diseases. (biomedcentral.com)
  • Much of the current knowledge about modifiers of conformational diseases has been gathered from linkage/association studies, candidate approaches, and unbiased genetic screens. (biomedcentral.com)
  • Although genetic variants identified in this way are enormously informative about pathways that affect disease processes and that can, when perturbed, modify disease phenotypes [ 25 - 30 ], they are likely to be different from the naturally occurring variations. (biomedcentral.com)
  • Duchenne muscular dystrophy (DMD) is a debilitating and fatal genetic disease affecting 1/3500 boys globally, characterized by progressive muscle breakdown and eventual death with an average lifespan in the mid-late twenties. (preprints.org)
  • Multiple system atrophy and CAG repeat length: a genetic screening of polyglutamine disease genes in Italian patients. (cdc.gov)
  • While some neurodegenerative diseases occur sporadically, others are caused by genetic mutations. (biologie-uni-siegen.de)
  • The genetic basis of HD is the expansion of a cysteine-adenosine-guanine (CAG) repeat encoding a polyglutamine tract in the N-terminus of the protein product called huntingtin. (medscape.com)
  • 35) in the first exon of the huntingtin ( HTT , IT15 ) gene 1 . (nature.com)
  • This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown. (preprints.org)
  • The huntingtin gene is widely expressed and is required for normal development. (thermofisher.com)
  • Variants (also called mutations) in the ATN1 gene can cause a very rare condition called congenital hypotonia, epilepsy, developmental delay, and digital anomalies (CHEDDA) syndrome. (medlineplus.gov)
  • Mutations in this gene have been found in patients with Renpenning syndrome 1 and other syndromes with X-linked cognitive disability. (nih.gov)
  • Another 150,000 people are believed to have mutations that cause the disease, but have not begun to show clinical symptoms. (scienceblog.com)
  • Huntington disease (HD), an autosomal dominant, progressive neurodegenerative disorder, is caused by an expanded CAG repeat sequence leading to an increase in the number of glutamine residues in the encoded protein 1 . (nature.com)
  • Methylation of mammalian DNA and histone residues are known to regulate transcription, and the discovery of demethylases that remove methylation in DNA and histones provide a basis for the understanding of dynamic regulation of mammalian gene expression. (cmbn.no)
  • The resulting gene product, a large protein called huntingtin, has an expanded stretch of polyglutamine residues, which accumulate within neurons and lead to disease via unknown mechanisms. (msdmanuals.com)
  • Both of these conditions are associated with a specific pathology, called a polyglutamine expansion (an amino acid repeat), which only occurs in SCAs and HD. (integratedhlth.co.uk)
  • These novel findings highlight a previously unknown mechanism causing disease which, importantly, suggests SAFB1 may be a diagnostic marker for polyglutamine expansion diseases, such as HD. (integratedhlth.co.uk)
  • A laboratory study indicates that the main protein involved in Parkinson's disease pathology does not behave as a prion when overexpressed. (neurodegenerationresearch.eu)
  • Interestingly, the same protein complex promotes pathology in other diseases including sporadic neurodegenerative diseases, suggesting that deregulation of common cellular pathways may contribute to development of otherwise unrelated diseases. (biologie-uni-siegen.de)
  • The same pathology was therefore not seen in control Parkinson's disease or multiple sclerosis. (integratedhlth.co.uk)
  • In fact, we know that in people with other diseases that involve the striatum such as Parkinson's disease, these symptoms are related to abnormal reward signals in the striatum. (hdsa.org)
  • Too little dopamine can lead to Parkinson's disease, a brain disorder that causes shaking and problems with movement and coordination. (neurodegenerationresearch.eu)
  • Turnbull, D. Ageing and Parkinson's disease: why is advancing age the biggest risk factor? (benthamscience.com)
  • Neuropsychiatric aspects of deep brain stimulation (DBS) for Parkinson's disease (PD) was the topic of several reports presented at the Congress. (medscape.com)
  • The phenotypes were comparable up to a deletion size of 7.1 Mb, and most features could be attributed to the terminally located gene DLL1 . (biomedcentral.com)
  • In the present review, the phenotypes of Met gene‑modified mice are summarized. (spandidos-publications.com)
  • Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder and is now also known as one of the CAG repeat (polyglutamine) diseases. (dehydrogenase-signal.com)
  • 2001). Histone deacetylase inhibitors reduce polyglutamine toxicity . (nih.gov)
  • Histone deacetylation and acetylation regulate the remodeling of chromatin framework and impact gene manifestation. (cancer-ecosystem.com)
  • While SBMA is relatively rare, recent studies have shown a significantly higher prevalence of the disease within the indigenous population of Western Canada compared to the general population. (preprints.org)
  • These observations suggest that the CIC-2 currents are affected in SBMA, an alteration that may contribute and potentially determine the pathophysiology of the disease. (kennedysdisease.org)
  • Zuo, L. Oxidative stress in neurodegenerative diseases: from molecular mechanisms to clinical applications. (benthamscience.com)
  • An in-depth knowledge of the cellular mechanisms that contribute to the disease development is a prerequisite for the development of therapeutic approaches. (biologie-uni-siegen.de)
  • CMBN shall take on a leading role in elucidating the role of DNA repair and genome maintenance mechanisms in preventing neurological disease and brain ageing. (cmbn.no)
  • He currently teaches courses on molecular systems biology that includes molecular mechanisms of human diseases and pharmacogenomics. (kgi.edu)
  • Differentially expressed genes (DEGs) in SCA2 SCs included abnormally expressed genes in SCs of ALS patients that may represent therapeutic targets for ALS and some that have potential as ALS or SCA2 biomarkers. (woofahs.com)
  • Evaluation of muscle and fat using MRI, in addition to biochemical indices such as serum creatinine level, are promising biomarkers to track the disease progression. (kennedysdisease.org)
  • Similarly, there are other diseases, for instance, in certain forms of amyotrophic lateral sclerosis, or ALS, there's a sequence GGGGCC, which gets copied too many times in the intron of its cognate gene. (mit.edu)
  • Nagafuchi S, Yanagisawa H, Ohsaki E, Shirayama T, Tadokoro K, Inoue T, Yamada M. Structure and expression of the gene responsible for the triplet repeat disorder, dentatorubral and pallidoluysian atrophy (DRPLA). (medlineplus.gov)
  • Involvement of other CAG-repeat genes has only been moderately investigated or reported, although an association was found with intermediate length in the ATXN1 in a small Italian cohort after discovery of a pedigree with co-occurrence of ALS and SCA1 disease. (videolectures.net)
  • The CAG repeat can either be located in the coding region or in the untranslated region of the respective genes. (biologie-uni-siegen.de)
  • The cause of the disease here is an expanded repeat. (mit.edu)
  • degeneration, the lesion distribution of which varies depending on the CAG repeat sizes in the causative gene. (dehydrogenase-signal.com)
  • Diagram Showing the Differences in the CAG Repeat Region Between a Healthy and Disease-Causing HTT Gene. (essex.ac.uk)
  • The large number of genes and the diversity of processes involved in the progression of neurological diseases in general, and HD in specific, emphasizes the need for comprehensive approaches in additional to studies of individual genes 14 . (nature.com)
  • First, these approaches are designed to identify individual modifier genes with strong phenotypic effects. (biomedcentral.com)
  • To identify disease modifier genes that may explain the neuroprotective effects of XBP1 deficiency, we performed gene expression profiling of brain cortex and striatum of these animals and uncovered insulin-like growth factor 2 (Igf2) as the major upregulated gene. (uchile.cl)
  • Genome-wide association studies have identified a firm link between the human FTO gene, obesity and type II diabetes. (cmbn.no)
  • In 1982, Harding et al reclassified the disease as X-linked bulbospinal neuronopathy to reflect the sensory conduction abnormalities noted in several of their cases. (medscape.com)
  • There is emerging awareness that both sleep and circadian rhythms abnormalities are associated with neurodegenerative diseases. (iospress.com)
  • Future experiments will focus on both the similarities between ATXN1 and ATXN2, such as TDP-43 binding capacity, as well as the differences, such as the CAT-interruptions in ATXN1, to further elucidate the role of polyglutamine expansions in ALS. (videolectures.net)
  • Recently, a form of precision medicine known as antisense therapy has gained traction as a promising therapeutic option for numerous neuromuscular diseases. (preprints.org)
  • Furthermore, the results of studies using HGF‑overexpressing mice have indicated the therapeutic potential of HGF for various types of disease and injury. (spandidos-publications.com)
  • The finding that polyglutamine toxicity in cell culture may be due to interference with nuclear factors has potential therapeutic implications, and research is underway to evaluate molecules with potential application as disruptors of that process. (nih.gov)
  • As well as identifying a possible diagnostic marker, these findings open up the possibility of developing new therapeutic treatments for these rare but devastating neurodegenerative diseases. (integratedhlth.co.uk)
  • therefore, gene activation will be of therapeutic benefit. (betadesks.com)
  • To address this, we examined the role of natural variation in defining the susceptibility of genetically diverse individuals to protein aggregation and toxicity, using the Caenorhabditis elegans polyglutamine model. (biomedcentral.com)
  • It allows users to obtain, visualize and prioritize molecular interaction networks using HD-relevant gene expression, phenotypic and other types of data obtained from human samples or model organisms. (nature.com)
  • We developed antisense oligonucleotides that suppressed AR gene expression in the periphery but not the CNS after subcutaneous administration. (nih.gov)
  • SC transcriptomes were decided using an SCA2 bacterial artificial chromosome mouse model expressing polyglutamine expanded expression. (woofahs.com)
  • Differentially expressed genes (DEGs) defined three interconnected pathways (innate immunity, fatty acid biosynthesis and cholesterol biosynthesis) in individual modules recognized by weighted gene co-expression network analysis. (woofahs.com)
  • Similarly, there have been few studies describing the expression of genes in the ALS SC (11,12). (woofahs.com)
  • Various growth factors, cytokines, and prostaglandins upregulate HGF gene expression, including basic fibroblast growth factor, oncostatin M, hypoxia-inducible factor 1α and nuclear factor-κB (NF-κB) ( 9 ). (spandidos-publications.com)
  • By contrast, transforming growth factor (TGF)-β1 was demonstrated to markedly downregulate HGF gene expression ( 10 , 11 ). (spandidos-publications.com)
  • and Applied Neurobiology36, 265-274 Immunohistological intensity measurements as a tool to assess sarcolemma-associated protein expression Aims: The quantification of protein levels in muscle biopsies is of particular relevance in the diagnostic process of neuromuscular diseases, but is difficult to assess in cases of partial protein deficiency, particularly when information on protein localization is required. (dehydrogenase-signal.com)
  • From 1999 to 2001, while on extended leave of absence from the University of Rochester, Dr. Ray directed research programs on regulation of gene expression and gene targeting at a plant biotechnology start-up company in San Diego. (kgi.edu)
  • Here we found that miR-19, miR-101 and miR-130 co-regulate ataxin1 levels and that their inhibition enhanced the cytotoxicity of polyglutamine-expanded ATXN1 in human cells. (nih.gov)
  • This study identifies IGF2 as a relevant factor deregulated in HD, operating as a disease modifier that buffers the accumulation of abnormal protein species. (uchile.cl)
  • Finally, some genes may have roles that are not relevant to laboratory conditions ( Peña-Castillo and Hughes, 2007 ). (biorxiv.org)
  • The scale for the assessment and rating of ataxia and the international cooperative ataxia rating scale were used to evaluate disease severity. (scielo.br)
  • A significant positive correlation between balance and disease severity was found. (scielo.br)
  • The level of the polyglutamine-expanded protein is one of the factors that contributes to disease severity. (nih.gov)
  • This fits with the hypothesis that intermediate polyglutamine expansions might not be causative but pose an increased risk for developing ALS. (videolectures.net)
  • Although taurine is considered a conditionally essential nutrient for humans and is thought to play a key role in several human diseases, clinical studies evaluating the effects of taurine are limited. (researchgate.net)
  • We also highlight how dysregulation of ubiquitin-mediated autophagy pathways is associated with a number of human diseases and the potential of targeting these pathways for disease intervention. (biomedcentral.com)