title: Chaperone-mediated autophagy in aging and neurodegeneration: lessons from alpha-synuclein.
abstract: Different conditions, ranging from genetic mutation to post-translational modification, result in the intracellular presence of misfolded or conformationally altered proteins. These abnormal proteins tend to organize in toxic oligomeric structures often resulting in cellular death. Alterations in the function of the surveillance systems that normally repair or remove abnormal proteins are the basis of many neurodegenerative disorders. In this review, we focus on such protein conformational disorders and on the role that altered function of intracellular proteolytic systems, in particular autophagy, plays in the evolution of these diseases. Using Parkinson disease as a main example, we recapitulate the different stages of this protein conformational disorder at the cellular level and relate them with changes in the different types of autophagy. Finally, we also comment on the effect that aggravating conditions, such as oxidative stress and aging, have on the functioning of the autophagic system and its ability to cope with altered proteins.
authors.affiliation: Department of Anatomy and Structural Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Urmi
authors.initials: U
authors.lastname: Bandyopadhyay
authors.forename: Urmi
authors.initials: U
authors.lastname: Bandhyopadhyay
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Cuervo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001343:Autophagy; D001921:Brain / Q000473:pathology; D006801:Humans; D018832:Molecular Chaperones / Q000502:physiology; D009410:Nerve Degeneration; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology; D011487:Protein Conformation; D017510:Protein Folding; D051844:alpha-Synuclein / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D018832:Molecular Chaperones; D051844:alpha-Synuclein