Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain.
The cause of neurodegeneration in Huntington's disease (HD) is unknown. Patients with HD have an expanded NH2-terminal polyglutamine region in huntingtin. An NH2-terminal fragment of mutant huntingtin was localized to neuronal intranuclear inclusions (NIIs) and dystrophic neurites (DNs) in the HD cortex and striatum, which are affected in HD, and polyglutamine length influenced the extent of huntingtin accumulation in these structures. Ubiquitin was also found in NIIs and DNs, which suggests that abnormal huntingtin is targeted for proteolysis but is resistant to removal. The aggregation of mutant huntingtin may be part of the pathogenic mechanism in HD.
DiFiglia
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M
Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Sapp
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E
Chase
K O
KO
Davies
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SW
Bates
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GP
Vonsattel
J P
JP
Aronin
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N
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001923:Brain Chemistry; D002467:Cell Nucleus / Q000737:chemistry; D002540:Cerebral Cortex / Q000737:chemistry; D003342:Corpus Striatum / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D016501:Neurites / Q000737:chemistry*; D009474:Neurons / Q000737:chemistry* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D014452:Ubiquitins / Q000032:analysis
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014452:Ubiquitins