TY - JOUR
T1 - Bid signal pathway components are identified in the temporal cortex with Parkinson disease
AU - Jiang, Hong
AU - He, Ping
AU - Adler, Charles H.
AU - Shill, Holly
AU - Beach, Thomas G.
AU - Li, Rena
AU - Shen, Yong
N1 - Funding Information:
The samples are from the Brain and Tissue Bank, Sun Health Research Institute. The BBDP is supported by the National Institute of Neurological Disorders and Stroke (U24NS072026 National Brain and Tissue Resource for PD and Related Disorders), the National Institute on Aging (P30AG19610 Arizona AD Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901, and 1001 to the Arizona PD Consortium), and the Michael J. Fox Foundation for Parkinson's Research.
Funding Information:
Study funding: Supported by National Institutes of Health (RO1AG025888, RO1AG032441), Alzheimer's Association IIRG-07-59510, and American Health Assistance Foundation (AHAF) grant G2006-118 and A2008-642.
PY - 2012/10/23
Y1 - 2012/10/23
N2 - Objective: Parkinson disease (PD), a devastating neurodegenerative disorder, affects motor abilities and cognition as well. It is not clear whether the proapoptotic protein, Bid, is involved in tumor necrosis factor death receptor I (TNFRI)-mediated destructive signal transduction pathways such as cell dysfunction or neurodegeneration in the temporal cortex of patients with PD. Methods: Molecular and biochemical approaches were used to dissect mitochondrial related components of the destructive signaling pathway in the temporal cortex from rapidly autopsied brains (postmortem interval mean 2.6 hours). Brains from patients with PD (n = 15) had an average age of 81.4 years, compared to the average age of 84.36 years in age-matched control patient brains (n = 15). Results: TNFRI and its adaptor protein, TRADD, were not only present in the cytoplasm of the temporal cortex, but were significantly elevated (42.3% and 136.1%, respectively) in PD brains compared to age-matched control brains. Bid in the PD temporal cortex could be further cleaved into tBid in the cytosol, which is translocated into the mitochondria, where cytochrome c is then released and caspase-3 is subsequently activated. Conclusion: Patients with PD have an activated Bid-mediated destructive signal pathway via TNFRI in the temporal cortex. Such deficits are pervasive, suggesting that they might contribute to cortex degeneration as PD manifests.
AB - Objective: Parkinson disease (PD), a devastating neurodegenerative disorder, affects motor abilities and cognition as well. It is not clear whether the proapoptotic protein, Bid, is involved in tumor necrosis factor death receptor I (TNFRI)-mediated destructive signal transduction pathways such as cell dysfunction or neurodegeneration in the temporal cortex of patients with PD. Methods: Molecular and biochemical approaches were used to dissect mitochondrial related components of the destructive signaling pathway in the temporal cortex from rapidly autopsied brains (postmortem interval mean 2.6 hours). Brains from patients with PD (n = 15) had an average age of 81.4 years, compared to the average age of 84.36 years in age-matched control patient brains (n = 15). Results: TNFRI and its adaptor protein, TRADD, were not only present in the cytoplasm of the temporal cortex, but were significantly elevated (42.3% and 136.1%, respectively) in PD brains compared to age-matched control brains. Bid in the PD temporal cortex could be further cleaved into tBid in the cytosol, which is translocated into the mitochondria, where cytochrome c is then released and caspase-3 is subsequently activated. Conclusion: Patients with PD have an activated Bid-mediated destructive signal pathway via TNFRI in the temporal cortex. Such deficits are pervasive, suggesting that they might contribute to cortex degeneration as PD manifests.
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U2 - 10.1212/WNL.0b013e3182703f76
DO - 10.1212/WNL.0b013e3182703f76
M3 - Article
C2 - 23019260
AN - SCOPUS:84870812045
SN - 0028-3878
VL - 79
SP - 1767
EP - 1773
JO - Neurology
JF - Neurology
IS - 17
ER -