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

Mayo Clinic Scottsdale (C.H.A.), Scottsdale, AZ
Neurology (Impact Factor: 8.29). 09/2012; 79(17):1767-73. DOI: 10.1212/WNL.0b013e3182703f76
Source: PubMed


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.
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).
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.
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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Available from: Rena Li, Feb 03, 2015
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    ABSTRACT: In Parkinson disease (PD), dopaminergic neuronal death within the substantia nigra generates characteristic motor manifestations, while synuclein pathology in cortical regions often causes additional symptoms, including cognitive impairment and dementia.(1) Therefore, a comprehensive understanding of PD pathogenesis requires the evaluation of cell death mechanisms both within the brainstem and extranigral sites. In the current issue of Neurology®, Jiang et al.(2) begin to reveal the potential molecular pathways responsible for cortical degeneration in PD.
    Neurology 09/2012; 79(17):1750-1. DOI:10.1212/WNL.0b013e31827040c6 · 8.29 Impact Factor