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Review
. 2020 Sep:190:111297.
doi: 10.1016/j.mad.2020.111297. Epub 2020 Jun 28.

Compounds that extend longevity are protective in neurodegenerative diseases and provide a novel treatment strategy for these devastating disorders

Sonja K Soo  1 , Paige D Rudich  1 , Annika Traa  1 , Namasthée Harris-Gauthier  1 , Hazel J Shields  1 , Jeremy M Van Raamsdonk  2
Affiliations
Review

Compounds that extend longevity are protective in neurodegenerative diseases and provide a novel treatment strategy for these devastating disorders

Sonja K Soo et al. Mech Ageing Dev. 2020 Sep.

Abstract

While aging is the greatest risk factor for the development of neurodegenerative disease, the role of aging in these diseases is poorly understood. In the inherited forms of these diseases, the disease-causing mutation is present from birth but symptoms appear decades later. This indicates that these mutations are well tolerated in younger individuals but not in older adults. Based on this observation, we hypothesized that changes taking place during normal aging make the cells in the brain (and elsewhere) susceptible to the disease-causing mutations. If so, then delaying some of these age-related changes may be beneficial in the treatment of neurodegenerative disease. In this review, we examine the effects of five compounds that have been shown to extend longevity (metformin, rapamycin, resveratrol, N-acetyl-l-cysteine, curcumin) in four of the most common neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis). While not all investigations observe a beneficial effect of these compounds, there are multiple studies that show a protective effect of each of these lifespan-extending compounds in animal models of neurodegenerative disease. Combined with genetic studies, this suggests the possibility that targeting the aging process may be an effective strategy to treat neurodegenerative disease.

Keywords: Aging; Alzheimer’s disease; Amyotrophic lateral sclerosis; Huntington’s disease; Parkinson’s disease.

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Figures

Figure 1.
Figure 1.. Lifespan-extending compounds can be protective in neurodegenerative diseases.
Five compounds that have been shown to increase lifespan in model organisms (metformin, resveratrol, rapamycin, N-acetyl cysteine, curcumin) have all been shown to have beneficial effects in four different neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis).
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