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Aggregate formation and synaptic abnormality induced by DSCR1
Author(s) -
Ma Hong,
Xiong Hui,
Liu Tong,
Zhang Lingyan,
Godzik Adam,
Zhang Zhuohua
Publication year - 2004
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 - 10.1046/j.1471-4159.2003.02294.x
Subject(s) - synaptophysin , neuropathology , huntingtin , pathogenesis , microtubule , microbiology and biotechnology , neuroscience , aggresome , chemistry , biology , disease , medicine , pathology , biochemistry , immunology , immunohistochemistry , huntington's disease , ubiquitin , gene
Aggregation of conformation‐abnormal peptides probably plays a key role in the pathogenesis of many neurodegenerative diseases. DSCR1 Down syndrome (DS) critical region 1, was identified from a chromosomal region (21q22.1‐q22.2) for the clinical manifestations of DS when an extra‐copy is present. We report that expression of DSCR1 in several cell types, including primary neurons, causes microtubule‐dependent aggresome‐like inclusion body formation. Disease‐associated huntingtin (Q148) and ataxin‐3 (Q84) co‐localize with DSCR1 aggregates. Neurons bearing DSCR1 aggregates show reduced synaptophysin staining in processes. DSCR1 residues 31–90 constitute an aggregation‐prone domain that is predicted to form a hydrophobic patch on the protein surface when residues 1–30 are removed. This study identifies a novel function of DSCR1 that may underlie DS neuropathology.