Augmenting brain metabolism to increase macro- and chaperone-mediated autophagy for decreasing neuronal proteotoxicity and aging

Progress in Neurobiology
Ben LoosEsther Wong

Abstract

Accumulation of toxic protein aggregates in the nerve cells is a hallmark of neuronal diseases and brain aging. Mechanisms to enhance neuronal surveillance to improve neuronal proteostasis have a direct impact on promoting neuronal health and forestalling age-related decline in brain function. Autophagy is a lysosomal degradative pathway pivotal for neuronal protein quality control. Different types of autophagic mechanisms participate in protein handling in neurons. Macroautophagy targets misfolded and aggregated proteins in autophagic vesicles to the lysosomes for destruction, while chaperone-mediated autophagy (CMA) degrades specific soluble cytosolic proteins delivered to the lysosomes by chaperones. Dysfunctions in macroautophagy and CMA contribute to proteo- and neuro-toxicity associated with neurodegeneration and aging. Thus, augmenting or preserving both autophagic mechanisms pose significant benefits in delaying physiological and pathological neuronal demises. Recently, life-style interventions that modulate metabolite ketone bodies, energy intake by caloric restriction and energy expenditure by exercise have shown to enhance both autophagy and brain health. However, to what extent these interventions affect neuronal au...Continue Reading

Citations

Apr 12, 2018·Physiology·Maria A Gonzalez PorrasCarlos B Mantilla
Mar 23, 2019·Nature Communications·Anuradha BhukelStephan J Sigrist
Feb 19, 2019·Behavioural Neurology·Mirjana Babić LekoGoran Šimić
Mar 28, 2019·Frontiers in Aging Neuroscience·David A Loeffler
Nov 14, 2018·Oxidative Medicine and Cellular Longevity·Senthilkumar SivanesanJayakumar Rajadas
Jan 29, 2019·Frontiers in Endocrinology·María Carolina BarbosaClaudio Marcelo Fader
Dec 9, 2020·Experimental Gerontology·Miguel Pareja-CajiaoCarlos B Mantilla
May 8, 2020·Mechanisms of Ageing and Development·Maria Sol Jacome Burbano, Eric Gilson
Jul 6, 2020·Biochimie·M PortovedoM Milanski

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