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

  • Cell Death and Disease
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Abstract

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.

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Acknowledgments

Support for this review was provided in part by grants from the NIH-NNDS, Parkinson’s Disease Foundation, and American Parkinson Disease Association.

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Authors and Affiliations

  1. Department of Neurology, Columbia University School of Medicine, New York, NY, USA

    Oren A. Levy

  2. Department of Pathology and Cell Biology, Columbia University School of Medicine, New York, NY, USA

    Cristina Malagelada & Lloyd A. Greene

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  1. Oren A. Levy
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  2. Cristina Malagelada
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Correspondence to Lloyd A. Greene.

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Levy, O.A., Malagelada, C. & Greene, L.A. Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps. Apoptosis 14, 478–500 (2009). https://doi.org/10.1007/s10495-008-0309-3

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