TY - JOUR
T1 - Chaperone-mediated autophagy in aging and neurodegeneration
T2 - Lessons from α-synuclein
AU - Bandhyopadhyay, Urmi
AU - Cuervo, Ana Maria
N1 - Funding Information:
We would like to gratefully acknowledge Ashish Massey for critically reviewing this manuscript and the other members of our laboratory for their valuable suggestions. Research in our laboratory is supported by National Institutes of Health/National Institute of Aging grants AG021904 and AG19834, a Huntington’s Disease Society of America Research grant and an Ellison Medical Foundation Award.
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
KW - Chaperones
KW - Lysosomes
KW - Parkinson disease
KW - Proteases
KW - Protein conformational disorders
UR - http://www.scopus.com/inward/record.url?scp=33845577972&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845577972&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2006.05.019
DO - 10.1016/j.exger.2006.05.019
M3 - Article
C2 - 16860504
AN - SCOPUS:33845577972
SN - 0531-5565
VL - 42
SP - 120
EP - 128
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 1-2
ER -