The ubiquitin-proteasome pathway in health and disease of the nervous system.
In recent years, proteolysis by the ubiquitin-proteasome pathway has attained prominence as a new molecular mechanism that regulates many vital functions of the nervous system, including development of synaptic connections and synaptic plasticity. Here, we review the latest findings on the role of proteolysis in sculpting the nervous system through control of axonal growth, axonal and dendritic pruning, and regulation of synaptic size and number. We also discuss how protein degradation functions in synaptic plasticity and the roles of local proteolysis in neuronal compartments. In addition, we describe how proteolysis is associated with Alzheimer's disease and ataxia. Furthermore, we highlight the recent approaches that exploit components of the ubiquitin-proteasome pathway for amelioration of these diseases in animal models.
Hegde
Ashok N
AN
Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA. ahegde@wfubmc.edu
Upadhya
Sudarshan C
SC
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001259:Ataxia / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D009420:Nervous System / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D025801:Ubiquitin / Q000502:physiology*
D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex