Natural Compounds and Autophagy: Allies Against Neurodegeneration

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 aggregateprone 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.

Modulation of Autophagy in Cancer Cells by Dietary Polyphenols

“…In addition, it has potential anti-cancer and chemopreventive effects. Both in vivo and in vitro studies confirm the effectiveness of PUN in the potential prevention of lung, breast, prostate, and colon cancers [ 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ].…”

“…Moreover, they have been suggested to play an important role in the prevention of cancer diseases [ 66 , 71 , 78 ]. The biologically active ingredients of fruits and vegetables, described in this review, such as the main catechin of green tea, EGCG [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ], oleuropein [ 49 , 50 , 51 , 52 , 53 ], punicalgin [ 39 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ], apigenin [ 40 , 77 , 78 , 79 , 80 ], resveratrol [ …”

“…The induction of AMPK-dependent autophagy by OL was noted in an experiment in an animal model of a C57BL/6J mouse [ 64 ]. Male and female mice were fed a high-fat and normal diet for eight weeks.…”

“…Increased expression of Beclin-1 , LC3B , and p62/Sqstm1 genes was observed in the study. However, OL had no significant effect on the expression of the apoptotic proteins Bcl-2 and caspase 3 in this animal model [ 64 ].…”

Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics

“…At molecular level, it has been suggested that resveratrol acts by inhibiting PDE [ 158 ] and thus increasing the cAMP level culminating in an increase of sirtuin 1 (SIRT1) and PGC1α protein activities which prevents axonal degeneration [ 159 ]. Moreover, resveratrol has been observed to induce the amelioration of mitochondrial activity in some neurodegenerative diseases [ 160 , 161 ].…”