title: Aging, protein aggregation, chaperones, and neurodegenerative disorders: mechanisms of coupling and therapeutic opportunities.
abstract: Late onset is a key unifying feature of human neurodegenerative maladies such as Alzheimer's and Parkinson's diseases and prion disorders. While sporadic cases typically emerge during the patient's seventh decade of life or later, mutation-linked, familial cases manifest during the fifth or sixth decade. This common temporal emergence pattern raises the prospect that slowing aging may prevent the accumulation of toxic protein aggregates that lead to the development of these disorders, postpone the onset of these maladies, and alleviate their symptoms once emerged. Invertebrate-based studies indicated that reducing the activity of insulin/IGF signaling (IIS), a prominent aging regulatory pathway, protects from neurodegeneration-linked toxic protein aggregation. The validity of this approach has been tested and confirmed in mammals as reducing the activity of the IGF-1 signaling pathway-protected Alzheimer's model mice from the behavioral and biochemical impairments associated with the disease. Here I review the recent advances in the field, describe the known mechanistic links between toxic protein aggregation and the aging process, and delineate the future therapeutic potential of IIS reduction as a treatment for various neurodegenerative disorders.
authors.affiliation: Biochemistry and Molecular Biology, The Institute of Medical Research Israel-Canada, The Hebrew University of Jerusalem-Hadassah Medical School, Ein Karem, Jerusalem, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Cohen
keywords: Aging; Alzheimer’s disease; insulin/IGF signaling; proteostasis
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