TY - JOUR
T1 - Autophagy and neurodegeneration
T2 - when the cleaning crew goes on strike
AU - Martinez-Vicente, Marta
AU - Cuervo, Ana Maria
N1 - Funding Information:
We thank the members of our lab for their comments and insightful discussions, and especially Ashish Massey for critically reading the manuscript. Work in our laboratory is supported by NIH/NIA grants AG021904 and AG25355, NIH/NINDS grant NS038370 and an Ellison Medical Foundation Award. We apologise to colleagues whose work has not been cited owing to space limitations.
PY - 2007/4
Y1 - 2007/4
N2 - Intracellular accumulation of altered and misfolded proteins is the basis of most neurodegenerative disorders. Altered proteins are usually organised in the form of toxic multimeric complexes that eventually promote neuronal death. Cells rely on surveillance mechanisms that take care of the removal of these toxic products. What then goes wrong in these pathologies? Recent studies have shown that a primary failure in autophagy, a mechanism for clearance of intracellular components in lysosomes, could be responsible for the accumulation of these altered proteins inside the affected neurons. In this Review we summarise our current knowledge on the contribution of autophagy to the maintenance of normal cellular homoeostasis, its changes in neurodegenerative disorders, and the role of aggravating factors such as oxidative stress and ageing on autophagic failure in these pathologies.
AB - Intracellular accumulation of altered and misfolded proteins is the basis of most neurodegenerative disorders. Altered proteins are usually organised in the form of toxic multimeric complexes that eventually promote neuronal death. Cells rely on surveillance mechanisms that take care of the removal of these toxic products. What then goes wrong in these pathologies? Recent studies have shown that a primary failure in autophagy, a mechanism for clearance of intracellular components in lysosomes, could be responsible for the accumulation of these altered proteins inside the affected neurons. In this Review we summarise our current knowledge on the contribution of autophagy to the maintenance of normal cellular homoeostasis, its changes in neurodegenerative disorders, and the role of aggravating factors such as oxidative stress and ageing on autophagic failure in these pathologies.
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U2 - 10.1016/S1474-4422(07)70076-5
DO - 10.1016/S1474-4422(07)70076-5
M3 - Review article
C2 - 17362839
AN - SCOPUS:33847652900
SN - 1474-4422
VL - 6
SP - 352
EP - 361
JO - Lancet Neurology
JF - Lancet Neurology
IS - 4
ER -