Abstract
Huntington's disease (HD) is one of a number of familial polyglutamine (polyQ) repeat diseases. These neurodegenerative disorders are caused by expression of otherwise unrelated proteins that contain an expansion of a polyQ tract, rendering them toxic to specific subsets of vulnerable neurons. These expanded repeats have an inherent propensity to aggregate; insoluble neuronal nuclear and cytoplasmic polyQ aggregates or inclusions are hallmarks of the disorders [1,2]. In HD, inclusions in diseased brains often precede onset of symptoms, and have been proposed to be involved in pathogenicity [3-5]. Various strategies to block the process of aggregation have been developed in an effort to create drugs that decrease neurotoxicity. A discussion of the effect of antibodies, caspase inhibitors, chemical inhibitors, heat-shock proteins, suppressor peptides and transglutaminase inhibitors upon aggregation and disease is presented.
MeSH terms
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Active Transport, Cell Nucleus / drug effects
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Animals
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal / therapeutic use
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / drug effects
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Caenorhabditis elegans Proteins / physiology
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Cysteine Proteinase Inhibitors / pharmacology
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Cysteine Proteinase Inhibitors / therapeutic use
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DNA Repeat Expansion*
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Drosophila Proteins / chemistry
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Drosophila Proteins / drug effects
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Drosophila Proteins / physiology
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Drug Design*
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Drug Evaluation, Preclinical
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Humans
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Huntingtin Protein
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Huntington Disease / drug therapy*
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Huntington Disease / genetics
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Intranuclear Inclusion Bodies / chemistry
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Intranuclear Inclusion Bodies / drug effects
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Mice
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Mice, Transgenic
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Mitochondria / drug effects
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Mitochondria / physiology
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Molecular Chaperones / drug effects
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Molecular Chaperones / physiology
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / drug effects*
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Nerve Tissue Proteins / genetics
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Nootropic Agents / pharmacology*
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Nootropic Agents / therapeutic use
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Nuclear Proteins / chemistry
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Nuclear Proteins / drug effects*
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Nuclear Proteins / genetics
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Peptides / genetics*
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Protein Conformation
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Protein Processing, Post-Translational / drug effects
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RNA Interference
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Repetitive Sequences, Amino Acid
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Transcription, Genetic / drug effects
Substances
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Antibodies, Monoclonal
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Caenorhabditis elegans Proteins
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Cysteine Proteinase Inhibitors
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Drosophila Proteins
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HTT protein, human
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Huntingtin Protein
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Molecular Chaperones
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Nerve Tissue Proteins
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Nootropic Agents
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Nuclear Proteins
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Peptides
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polyglutamine