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Neurodegenerative disorders

A neuroprotective role for α-synuclein

Nature Reviews Neuroscience volume 7, page 5 (2006)Cite this article

A central role for α-synuclein in neurodegenerative conditions has long been apparent: mutations or triplication of the gene cause severe Parkinson's disease, and inclusion bodies containing the protein are found in Parkinson's disease, Alzheimer's disease and other neurodegenerative 'synucleinopathies'. However, despite its involvement in pathology, the normal physiological function of α-synuclein, which is enriched in presynaptic nerve terminals, has remained an enigma. New work from the laboratory of Thomas Sudhof reveals an unexpected neuroprotective role for α-synuclein in a progressive neurodegenerative mouse model caused by deletion of cysteine-string protein-α (CSPα).

CSPα is a molecular chaperone, abundant at presynaptic nerve terminals, deletion of which results in early-onset neurodegeneration and lethality in mice by 1–4 months of age. Similarly, overexpression of human α-synuclein leads to a progressive, but late-onset, neurodegenerative phenotype. Intrigued by an apparent overlap in the localization of α-synuclein and CSPα, and a possible complementarity of their functions, Chandra and colleagues investigated the relationship between the neurodegenerative phenotypes associated with each protein, crossing transgenic α-synuclein mice with CSPα-knockout mice.

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ORIGINAL RESEARCH PAPER

  1. Chandra S. et al. α-Synuclein cooperates with CSPα in preventing neurodegeneration. Cell 123, 383–396 (2005)

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Authors
  1. Daniel McGowan
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McGowan, D. A neuroprotective role for α-synuclein. Nat Rev Neurosci 7, 5 (2006). https://doi.org/10.1038/nrn1834

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  • DOI: https://doi.org/10.1038/nrn1834

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