TY - JOUR
T1 - Selective manipulation of aging
T2 - A novel strategy for the treatment of neurodegenerative disorders
AU - Moll, Lorna
AU - El-Ami, Tayir
AU - Cohen, Ehud
PY - 2014/2/13
Y1 - 2014/2/13
N2 - Aging is the major risk factor for the development of human neurodegenerative maladies such as Alzheimer's, Huntington's and Parkinson's diseases, and prion disorders, all of which stem from toxic protein aggregation. Although sporadic cases typically onset during the patient's seventh decade of life or later, mutation-linked, familial disorders manifest during the fifth or sixth decade of life. This common temporal emergence pattern suggests that slowing aging can postpone the onset of these maladies and alleviate their symptoms once emerged. Studies in worms and flies that express disease-linked aggregative proteins revealed that reducing the activity of the insulin / insulin-like growth factor (IGF) signalling (IIS), a prominent aging regulatory pathway, protects these animals from toxic protein aggregation. The therapeutic potential of this approach has been tested and confirmed in mammals as reducing the activity of the IGF1 signalling cascade partially protects Alzheimer's-model mice from premature death, and behavioural and pathological impairments associated with the disorder. Here we review the recent advances in the field, describe the known mechanistic links between toxic protein aggregation, neurodegenerative disorders and the aging process and delineate recent studies that point at IGF1 signalling inhibitors as promising therapies for the treatment of various late-onset neurodegenerative disorders.
AB - Aging is the major risk factor for the development of human neurodegenerative maladies such as Alzheimer's, Huntington's and Parkinson's diseases, and prion disorders, all of which stem from toxic protein aggregation. Although sporadic cases typically onset during the patient's seventh decade of life or later, mutation-linked, familial disorders manifest during the fifth or sixth decade of life. This common temporal emergence pattern suggests that slowing aging can postpone the onset of these maladies and alleviate their symptoms once emerged. Studies in worms and flies that express disease-linked aggregative proteins revealed that reducing the activity of the insulin / insulin-like growth factor (IGF) signalling (IIS), a prominent aging regulatory pathway, protects these animals from toxic protein aggregation. The therapeutic potential of this approach has been tested and confirmed in mammals as reducing the activity of the IGF1 signalling cascade partially protects Alzheimer's-model mice from premature death, and behavioural and pathological impairments associated with the disorder. Here we review the recent advances in the field, describe the known mechanistic links between toxic protein aggregation, neurodegenerative disorders and the aging process and delineate recent studies that point at IGF1 signalling inhibitors as promising therapies for the treatment of various late-onset neurodegenerative disorders.
KW - Aging
KW - Insulin/IGF signalling
KW - Neurodegenerative disorders
KW - Proteostasis
KW - Proteotoxicity
UR - http://www.scopus.com/inward/record.url?scp=84899729969&partnerID=8YFLogxK
U2 - 10.4414/smw.2014.13917
DO - 10.4414/smw.2014.13917
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C2 - 24526357
AN - SCOPUS:84899729969
SN - 1424-7860
VL - 144
JO - Swiss Medical Weekly
JF - Swiss Medical Weekly
M1 - w13917
ER -