Cell death pathways in Parkinson's disease: proximal triggers, distal effectors, and final steps

Parkinson's disease (PD) is a common neurodegenerative disorder. Neuronal cell death in PD is still poorly understood, despite a wealth of potential pathogenic mechanisms and pathways. Defects in several cellular systems have been implicated as early triggers that start cells down the road towa...

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Bibliographic Details
Published in:Apoptosis (London) 2009-04, Vol.14 (4), p.478-500
Main Authors: Levy, Oren A, Malagelada, Cristina, Greene, Lloyd A
Format: Article
Language:English
Subjects:
alpha-Synuclein - metabolism
Animals
Apoptosis - physiology
Biochemistry
Biodegradation
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell Biology
Cell Death
Cell Death and Disease
Humans
Mortality
Oncology
Oxidative stress
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson Disease - physiopathology
Parkinson's disease
Signal Transduction - physiology
Virology
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Summary:Parkinson's disease (PD) is a common neurodegenerative disorder. Neuronal cell death in PD is still poorly understood, despite a wealth of potential pathogenic mechanisms and pathways. Defects in several cellular systems have been implicated as early triggers that start cells down the road toward neuronal death. These include abnormal protein accumulation, particularly of alpha-synuclein; altered protein degradation via multiple pathways; mitochondrial dysfunction; oxidative stress; neuroinflammation; and dysregulated kinase signaling. As dysfunction in these systems mounts, pathways that are more explicitly involved in cell death become recruited. These include JNK signaling, p53 activation, cell cycle re-activation, and signaling through bcl-2 family proteins. Eventually, neurons become overwhelmed and degenerate; however, even the mechanism of final cell death in PD is still unsettled. In this review, we will discuss cell death triggers and effectors that are relevant to PD, highlighting important unresolved issues and implications for the development of neuroprotective therapies.
ISSN:1360-8185
1573-675X
DOI:10.1007/s10495-008-0309-3