Ageing and protein aggregation-mediated disorders: from invertebrates to mammals.
Late onset is a common hallmark character of numerous disorders including human neurodegenerative maladies such as Huntington's, Parkinson's and Alzheimer's diseases. Why these diseases manifest in aged individuals and why distinct disorders share strikingly similar emergence patterns were until recently unsolved enigmas. During the past decade, invertebrate-based studies indicated that the insulin/IGF signalling pathway (IIS) mechanistically links neurodegenerative-associated toxic protein aggregation and ageing; yet, until recently it was unclear whether this link is conserved from invertebrates to mammals. Recent studies performed in Alzheimer's mouse models indicated that ageing alteration by IIS reduction slows the progression of Alzheimer's-like disease, protects the brain and mitigates the behavioural, pathological and biochemical impairments associated with the disease. Here, we review these novel studies and discuss the potential of ageing alteration as a therapeutic approach for the treatment of late onset neurodegeneration.
Howard Hughes Medical Institute, Glenn Center for Ageing Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies , 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. dillin@salk.edu
Andrew
A
Dillin
Ehud
E
Cohen
D017668:Age of Onset; D000375:Aging / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism
D007328:Insulin; D013002:Somatomedins