The Ubiquitin Proteasome System in Neurodegenerative Diseases

  • Ciechanover A
  • Brundin P
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Abstract

The ubiquitin-proteasome system targets numerous cellular proteins for degradation. In addition, modifications by ubiquitin-like proteins as well as proteins containing ubiquitin-interacting and -associated motifs modulate many others. This tightly controlled process involves multiple specific and general enzymes of the system as well as many modifying and ancillary proteins. Thus, it is not surprising that ubiquitin-mediated degradation/processing/modification regulates a broad array of basic cellular processes. Moreover, aberrations in the system have been implicated, either as a primary cause or secondary consequence, in the pathogenesis of both inherited and acquired neurodegenerative diseases. Recent findings indicate that the system is involved in the pathogenesis of Parkinson's, Alzheimer's, Huntington's, and Prion diseases as well as amyotrophic lateral sclerosis. This raises hopes for a better understanding of the pathogenetic mechanisms involved in these diseases and for the development of novel, mechanism-based therapeutic modalities.

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Ciechanover, A., & Brundin, P. (2004). The Ubiquitin Proteasome System in Neurodegenerative Diseases. Neuron, 40(2), 427–446. https://doi.org/10.1016/s0896-6273(03)00606-8

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