α-Synuclein Promotes Neuroprotection Through NF-κB–Mediated Transcriptional Regulation of Protein Kinase Cδ

Sci. Signal., 18 October 2011
Vol. 4, Issue 195, p. jc6
DOI: 10.1126/scisignal.2002425

α-Synuclein Promotes Neuroprotection Through NF-κB–Mediated Transcriptional Regulation of Protein Kinase Cδ

  1. Reina Aoki1,* and
  2. Yun Rose Li1,2,*,
  1. 1The authors are graduate students in the Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  2. 2Medical Scientist Training Program and Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  3. *These authors contributed equally to this manuscript.
  1. Corresponding author. E-mail: liyun{at}mail.med.upenn.edu

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder that results in a progressively debilitating loss of motor function and hypokinesia and is characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Recent evidence suggests that caspase-3–dependent proteolytic cleavage and nuclear translocation of the δ isoform of protein kinase C (PKCδ) may be required for oxidative stress–induced dopaminergic cell death. Whereas several proteins have been postulated to contribute to dopaminergic neuron loss, the signaling cascades that mediate this selective neuron loss in PD are not well understood. The presynaptic protein α-synuclein (α-syn), mutations in which cause familial PD, has been implicated in pathways that influence both neuronal protection and apoptosis. However, the activities of α-syn in PD have not been elucidated at the molecular level, and whether α-syn is neuroprotective or neurotoxic remains controversial. This Journal Club discusses recent research indicating that α-syn may protect against dopaminergic cell death by down-regulating PKCδ, a key molecule that mediates apoptosis in these cells. These findings are the first steps toward the understanding of critical signaling pathways that might be important in PD pathogenesis and represent potential targets for developing new therapies.

Citation:

R. Aoki and Y. R. Li, α-Synuclein Promotes Neuroprotection Through NF-κB–Mediated Transcriptional Regulation of Protein Kinase Cδ. Sci. Signal. 4, jc6 (2011).
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