, Volume 14, Issue 4, pp 478–500 | Cite as

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

  • Oren A. Levy
  • Cristina Malagelada
  • Lloyd A. Greene
Cell Death and Disease


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.


Parkinson’s disease Apoptosis Neuroprotection Alpha-synuclein 



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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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Oren A. Levy
    • 1
  • Cristina Malagelada
    • 2
  • Lloyd A. Greene
    • 2
  1. 1.Department of NeurologyColumbia University School of MedicineNew YorkUSA
  2. 2.Department of Pathology and Cell BiologyColumbia University School of MedicineNew YorkUSA

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