Selective manipulation of aging: a novel strategy for the treatment of neurodegenerative disorders

• Published in: Swiss medical weekly Vol. 144; no. 708; p. w13917
• Main Authors: Moll, Lorna, El-Ami, Tayir, Cohen, Ehud
• Format: Journal Article
• Language: English
• Published: Switzerland SMW supporting association (Trägerverein Swiss Medical Weekly SMW) 13.02.2014
• Subjects: aging; Aging - metabolism; Animals; Brain - metabolism; Homeostasis; Humans; Insulin - metabolism; Insulin-Like Growth Factor I - antagonists & inhibitors; Insulin-Like Growth Factor I - metabolism; insulin/IGF signalling; Neurodegenerative Diseases - etiology; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - therapy; neurodegenerative disorders; proteostasis; proteotoxicity; Signal Transduction - genetics; Signal Transduction - physiology
• ISSN: 1424-7860; 1424-3997
• DOI: 10.4414/smw.2014.13917

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.