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Huntington disease (HD) is an inherited neurodegenerative disorder caused by an expansion of the CAG repeat region in the first exon of the huntingtin (Htt) gene. Neurodegeneration, which begins in the striatum and then spreads to other brain areas, is preceded by dysfunction in multiple aspects of neurotransmission across a variety of brain areas. This review will provide an overview of the neurochemical mediators and modulators of synaptic transmission that are disrupted in HD. This includes classical neurotransmitters like glutamate and GABA, modulators such as dopamine, adenosine and endocannabinoids, and molecules like brain-derived neurotrophic factor (BDNF) which affect neurotransmission in a more indirect manner. Alterations in the functioning of these signaling pathways can occur across multiple brain regions such as striatum, cortex and hippocampus, and affect transmission and plasticity at the synapses within these regions, which may ultimately change behaviour and contribute to the pathophysiology of HD. The current state of knowledge in this area has already yielded useful information about the causes of synaptic dysfunction and selective cell death. A full understanding of the mechanisms and consequences of disruptions in synaptic function and plasticity will lend insight into the development of the symptoms of HD, and potential drug targets for ameliorating them. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: Journal of neurochemistry
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This study will evaluate the safety of 3 months of Dimebon dosing and the efficacy of Dimebon in improving cognitive, motor, and overall function in subjects with Huntington's Disease.
The purpose of this trial is to study early brain and behavioral changes in people who have the gene expansion for Huntington's disease, but are currently healthy and have no symptoms.
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A neuronal protein consisting of three PDZ DOMAINS, an SH3 DOMAIN, and a C-terminal guanylate kinase-like region (see MAGUK PROTEINS). It localizes to the POST-SYNAPTIC DENSITY and associates with the cytoplasmic tail of NMDA RECEPTORS and SHAKER POTASSIUM CHANNELS, playing a critical role in NMDA receptor-mediated SYNAPTIC PLASTICITY.
A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION, POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.
Cytoskeleton specialization at the cytoplasmic side of postsynaptic membrane in SYNAPSES. It is involved in neuronal signaling and NEURONAL PLASTICITY and comprised of GLUTAMATE RECEPTORS; scaffolding molecules (e.g., PSD95, PSD93), and other proteins (e.g., CaCMKII).
The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.
Serine/threonine protein kinase responsible for various SKELETAL MUSCLE functions; HEART CONDUCTION SYSTEM activity; calcium HOMEOSTASIS; calcium uptake by SARCOPLASMIC RETICULUM and SYNAPTIC PLASTICITY. It is encoded by the DMPK gene and its abnormal EXPANDED TRINUCLEOTIDE REPEAT of CTG in the 3'-UTR is associated with MYOTONIC DYSTROPHY 1.
Huntington's disease is a hereditary disease caused by a defect in a single gene on Chromosome 4 that is inherited in an autosomal dominant fashion. The defect causes a part of DNA, called a CAG repeat, to occur many more times than it is supposed to...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...