Autophagy and its possible roles in nervous system diseases, damage and repair.
Increased numbers of autophagosomes/autophagic vacuoles are seen in a variety of physiological and pathological states in the nervous system. In many cases, it is unclear if this phenomenon is the result of increased autophagic activity or decreased autophagosome-lysosome fusion. The functional significance of autophagy and its relationship to cell death in the nervous system is also poorly understood. In this review, we have considered these issues in the context of acute neuronal injury and a range of chronic neurodegenerative conditions, including the Lurcher mouse, Alzheimer's, Parkinson's, Huntington's and prion diseases. While many issues remain unresolved, these conditions raise the possibility that autophagy can have either deleterious or protective effects depending on the specific situation and stage in the pathological process.
Rubinsztein
David C
DC
Departments of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, UK. dcr1000@cus.cam.ac.uk
DiFiglia
Marian
M
Heintz
Nathaniel
N
Nixon
Ralph A
RA
Qin
Zheng-Hong
ZH
Ravikumar
Brinda
B
Stefanis
Leonidas
L
Tolkovsky
Aviva
A
D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D009474:Neurons / Q000473:pathology*; D010300:Parkinson Disease / Q000473:pathology*; D010455:Peptides / Q000378:metabolism; D010588:Phagosomes / Q000473:pathology*; D017096:Prion Diseases / Q000473:pathology*
D010455:Peptides; C097188:polyglutamine