Natural Compounds and Autophagy: Allies Against Neurodegeneration

Alessandra Stacchiotti, Giovanni Corsetti, Alessandra Stacchiotti, Giovanni Corsetti

Abstract

Prolonging the healthy life span and limiting neurological illness are imperative goals in gerontology. Age-related neurodegeneration is progressive and leads to severe diseases affecting motility, memory, cognitive function, and social life. To date, no effective treatments are available for neurodegeneration and irreversible neuronal loss. Bioactive phytochemicals could represent a natural alternative to ensure active aging and slow onset of neurodegenerative diseases in elderly patients. Autophagy or macroautophagy is an evolutionarily conserved clearing process that is needed to remove aggregate-prone proteins and organelles in neurons and glia. It also is crucial in synaptic plasticity. Aberrant autophagy has a key role in aging and neurodegeneration. Recent evidence indicates that polyphenols like resveratrol and curcumin, flavonoids, like quercetin, polyamine, like spermidine and sugars, like trehalose, limit brain damage in vitro and in vivo. Their common mechanism of action leads to restoration of efficient autophagy by dismantling misfolded proteins and dysfunctional mitochondria. This review focuses on the role of dietary phytochemicals as modulators of autophagy to fight Alzheimer's and Parkinson's diseases, fronto-temporal dementia, amyotrophic lateral sclerosis, and psychiatric disorders. Currently, most studies have involved in vitro or preclinical animal models, and the therapeutic use of phytochemicals in patients remains limited.

Keywords: Alzheimer’s disease; Parkinson’s disease; alkaloids; autophagy; polyphenols; spermidine; terpenes; trehalose.

Copyright © 2020 Stacchiotti and Corsetti.

Figures

FIGURE 1
FIGURE 1
Macroautophagy signaling in the mammalian brain. It consists in three main phases: formation-elongation of a round structure, maturation then its content degradation-recycling. The first step of autophagy starts in the cytoplasm with the “phagophore,” a peculiar double membrane structure derived from ER, Golgi complex or plasmalemma that subsequently elongates, and closes on itself to produce an “autophagosome,” filled with proteins or lipidic material and damaged organelles. Then the “autophagosome” progressively matures and merges with lysosomes becoming an “autolysosome” or “amphisome”to complete clearing. In the last final step, all cargo is dismantled by acidic lysosomal hydrolases and eventually a new phagophore is reformed. Major regulators of different phases are class III PI3-K complex and Beclin 1 protein, Atg proteins cascade resulting in Atg3/Atg7 mediated LC3I into LC3II conversion as indicated and discussed in the text. Extensive details on macroautophagy machinery are reported by Feng et al. (2014).

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Source: PubMed

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