Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases

Front Aging Neurosci. 2016 Dec 15;8:303. doi: 10.3389/fnagi.2016.00303. eCollection 2016.


The ubiquitin-proteasome system (UPS) is one of the major protein degradation pathways, where abnormal UPS function has been observed in cancer and neurological diseases. Many neurodegenerative diseases share a common pathological feature, namely intracellular ubiquitin-positive inclusions formed by aggregate-prone neurotoxic proteins. This suggests that dysfunction of the UPS in neurodegenerative diseases contributes to the accumulation of neurotoxic proteins and to instigate neurodegeneration. Here, we review recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.

Keywords: Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; deubiquitinating enzyme; proteasome; ubiquitin.

Publication types

  • Review