Antioxidant Modulation of mTOR and Sirtuin Pathways in Age-Related Neurodegenerative Diseases

Mol Neurobiol. 2020 Dec;57(12):5193-5207. doi: 10.1007/s12035-020-02083-1. Epub 2020 Aug 31.

Abstract

In the human body, cell division and metabolism are expected to transpire uneventfully for approximately 25 years. Then, secondary metabolism and cell damage products accumulate, and ageing phenotypes are acquired, causing the progression of disease. Among these age-related diseases, neurodegenerative diseases have attracted considerable attention because of their irreversibility, the absence of effective treatment and their relationship with social and economic pressures. Mechanistic (formerly mammalian) target of rapamycin (mTOR), sirtuin (SIRT) and insulin/insulin growth factor 1 (IGF1) signalling pathways are among the most important pathways in ageing-associated conditions, such as neurodegeneration. These longevity-related pathways are associated with a diversity of various processes, including metabolism, cognition, stress reaction and brain plasticity. In this review, we discuss the roles of sirtuin and mTOR in ageing and neurodegeneration, with an emphasis on their regulation of autophagy, apoptosis and mitochondrial energy metabolism. The intervention of neurodegeneration using potential antioxidants, including vitamins, phytochemicals, resveratrol, herbals, curcumin, coenzyme Q10 and minerals, specifically aimed at retaining mitochondrial function in the treatment of Alzheimer's disease, Parkinson's disease and Huntington's disease is highlighted.

Keywords: Ageing; Antioxidants; Neurodegenerative diseases; Sirtuins; mTOR.

Publication types

  • Review

MeSH terms

  • Aging / pathology*
  • Animals
  • Antioxidants / metabolism*
  • Humans
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology*
  • Signal Transduction*
  • Sirtuins / metabolism*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Antioxidants
  • TOR Serine-Threonine Kinases
  • Sirtuins