Autophagy and the ubiquitin-proteasome system: Collaborators in neuroprotection

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1782

Review

Nedelsky, Natalia B.^1,2  Todd, Peter K.^2,3  Taylor, J. Paul^1,2 

[1] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA

[2] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA

[3] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA

关键词: Autophagy;    Ubiquitin-proteosome system;    Neurodegeneration;    HDAC6;    p62;   

DOI  :  10.1016/j.bbadis.2008.10.002

来源: Elsevier

【 摘 要 】

Protein degradation is an essential cellular function that, when dysregulated or impaired, can lead to a wide variety of disease states. The two major intracellular protein degradation systems are the ubiquitin-proteasome system (UPS) and autophagy, a catabolic process that involves delivery of cellular components to the lysosome for degradation. While the UPS has garnered much attention as it relates to neurodegenerative disease, important links between autophagy and neurodegeneration have also become evident. Furthermore, recent Studies have revealed interaction between the UPS and autophagy, Suggesting a coordinated and complementary relationship between these degradation systems that becomes critical in times of cellular stress. Here we describe autophagy and review evidence implicating this system as all important player in the Pathogenesis of neurodegenerative disease. We discuss the role of autophagy in neurodegeneration and review its neuroprotective functions as revealed by experimental manipulation in disease models. Finally, we explore potential parallels and connections between autophagy and the UPS, highlighting their collaborative roles in protecting against neurodegenerative disease. (C) 2008 Elsevier B.V. All rights reserved.

【 授权许可】

Free