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Neuroprotective properties of Bcl‐w in Alzheimer disease
Author(s) -
Zhu Xiongwei,
Wang Yang,
Ogawa Osamu,
Lee Hyounggon,
Raina Arun K.,
Siedlak Sandra L.,
Harris Peggy L. R.,
Fujioka Hisashi,
Shimohama Shun,
Tabaton Massimo,
Atwood Craig S.,
Petersen Robert B.,
Perry George,
Smith Mark A.
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 - 10.1111/j.1471-4159.2004.02416.x
Subject(s) - neuroprotection , staurosporine , apoptosis , neurodegeneration , programmed cell death , biology , cytoplasm , alzheimer's disease , neuroscience , microbiology and biotechnology , degenerative disease , senile plaques , pathology , disease , medicine , signal transduction , central nervous system disease , protein kinase c , biochemistry
While there is a host of pro‐apoptotic stimuli that target neurons in Alzheimer disease (AD), given the chronicity of the disease and the survival of many neurons, those neurons must either avoid or, at minimum, delay apoptotic death signaling. In this study, we investigated Bcl‐w, a novel member of the Bcl‐2 family that promotes cell survival. In AD, we found increased levels of Bcl‐w associated with neurofibrillary pathology and punctate intracytoplasmic structures whereas, in marked contrast, there are only low diffuse levels of Bcl‐w in the neuronal cytoplasm of age‐matched control cases. Immunoblot analysis confirmed that Bcl‐w levels were significantly increased in AD. By electron microscopy, we determined that the increased Bcl‐w expression in AD was ultrastructurally localized to mitochondria and neurofibrillary pathology. To investigate the cause and consequence of Bcl‐w up‐regulation in neurons, we found that fibrillized amyloid‐β led to increased Bcl‐w protein levels in M17 human neuroblastoma cells, and that overexpression of Bcl‐w significantly protected neurons against staurosporine‐ and amyloid‐β‐induced apoptosis. Taken together, these series of results suggest that Bcl‐w may play an important protective role in neurons in the diseased brain and that this aspect could be therapeutically harnessed to afford neuroprotection.