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Amyloid β peptide binds a novel death‐inducing protein, AB‐DIP
Author(s) -
Lakshmana Madepalli K.,
Araki Wataru,
Tabira Takeshi
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-3672fje
Subject(s) - gene knockdown , neurotoxicity , chemistry , microbiology and biotechnology , programmed cell death , peptide , small interfering rna , apoptosis , amyloid precursor protein , biology , alzheimer's disease , rna , biochemistry , medicine , gene , toxicity , disease , organic chemistry
Amyloid β‐peptide (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD). It is toxic to neurons, but the mechanism for its action remains largely unknown. Here, we have identified a novel death‐inducing protein, Aβ‐related DIP (AB‐DIP), by two‐hybrid screening of the human brain cDNA library and confirmed the binding of Aβ with AB‐DIP by coimmunoprecipitation. Overexpression of AB‐DIP‐induced cell death and coexpression of Aβ enhanced the cell death. During apoptosis, the 97‐kDa AB‐DIP was cleaved to a 62‐kDa protein (AB‐DIP p62) at the caspase cleavage site, LEKD. It is more important that cotransfection of Aβ with AB‐DIP produced the AB‐DIP p62 fragment. Small interfering RNA‐mediated knockdown of AB‐DIP protein expression significantly protected neuroblastoma cells from Aβ‐induced neurotoxicity. AB‐DIP may mediate the neurotoxicity of Aβ, and therefore, AB‐DIP may be a potential, therapeutic target for AD.