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Neurology. 2012 Oct 23;79(17):1767-73. doi: 10.1212/WNL.0b013e3182703f76. Epub 2012 Sep 26.

Bid signal pathway components are identified in the temporal cortex with Parkinson disease.

Author information

1
Sun Health Research Institute, Sun City, AZ, USA.

Abstract

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.

PMID:
23019260
PMCID:
PMC3475620
DOI:
10.1212/WNL.0b013e3182703f76
[Indexed for MEDLINE]
Free PMC Article

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