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Loss of SNAP‐25 and rabphilin 3a in sensory‐motor cortex in Huntington’s disease
Author(s) -
Smith Ruben,
Klein Pontus,
KocSchmitz Yeliz,
Waldvogel Henry J.,
Faull Richard L.M.,
Brundin Patrik,
Plomann Markus,
Li JiaYi
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04703.x
Subject(s) - syntaxin , synaptophysin , neurotransmitter , snap , huntingtin , snare complex , biology , synaptobrevin , synaptic vesicle , neuroscience , synaptotagmin 1 , medicine , huntington's disease , synapsin , endocrinology , immunohistochemistry , disease , central nervous system , immunology , biochemistry , vesicle , exocytosis , computer graphics (images) , membrane , secretion , computer science
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG‐expansion in the gene encoding the protein huntingtin. The disease is characterized by progressive motor disturbances, cognitive defects, dementia, and weight loss. Using western blotting and immunohistochemistry we have assessed the expression levels and patterns of a number of proteins involved in neurotransmitter release in post‐mortem frontal cortex samples from 10 HD cases with different disease grades. We report a loss of the soluble N ‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) protein, synaptosome‐associated protein 25 (SNAP 25) in HD brains of grades I–IV. Moreover, in brains of grade III and IV we found a reduction in rabphilin 3a, a protein involved in vesicle docking and recycling. These losses appear to be specific and not due to a general loss of synapses in the HD cortex. Thus, levels of synaptobrevin II, syntaxin 1, rab3a or synaptophysin are unaltered in the same patient samples. SNAP 25 and rabphilin 3a are crucial for neurotransmitter release. Therefore, we suggest that a deficient pre‐synaptic transmitter release may underlie some of the symptoms of HD.