Emerging Potential of Naturally Occurring Autophagy Modulators Against Neurodegeneration

Abstract

Background: Naturally-occurring products derived from living organisms have been shown to modulate various pharmacological and biological activities. Natural products protect against various diseases, which could be used for therapeutic assistance. Autophagy, a lysosome-mediated self-digestion pathway, has been implicated in a range of pathophysiological conditions and has recently gained attention for its role in several neurodegenerative diseases. Methods: In this current review, we emphasized the recent progress made in our understanding of the molecular mechanism of autophagy in different cellular and mouse models using naturally-occurring autophagy modulators for the management of several neurodegenerative diseases. Results: Accumulating evidence has revealed that a wide variety of natural compounds such as alkaloids, polyphenols, terpenoids, xanthonoids, flavonoids, lignans, disaccharides, glycolipoproteins, and saponins are involved in the modulation of the autophagy signaling pathway. These natural products have been used to treat various neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, spinocerebellar ataxia, neuroblastoma, and glioblastoma. Although a number of synthetic autophagy regulators have been recognized as encouraging neurodegenerative therapeutic candidates, natural autophagy- regulating compounds have been of further interest as potential disease therapeutics, as they cause insignificant side effects. Conclusion: Existing in vitro and in vivo data are promising and highlight that naturally-occurring autophagyregulating compounds play an important role in the prevention and treatment of neurodegenerative disorders.

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

“…Alzheimer's disease (AD) is a form of dementia that most commonly affects older people and is characterized by progressive cognitive decline, which usually starts with a decrease in memory [1,2]. AD is characterized by profound oxidative stress, synaptic connection loss from a specific brain regions, cumulative emergence of intracellular tau pathology, and buildup of extracellular amyloid beta (Aβ) plaques [3,4]. The harmful activities of free radicals and oxidized metabolites in AD include DNA oxidation, lipid peroxidation, and protein oxidation, which ultimately leads to neuronal death [5][6][7][8].…”

Natural Compounds and Autophagy: Allies Against Neurodegeneration

“…Nevertheless, there is wide consensus on the efficacy of natural pleiotropic compounds able to enhance or restored insufficient autophagy in aggregated-prone proteins pathologies like AD, PD, HD in preclinical rodent models (Djajadikerta et al, 2019;Rahman et al, 2020). Remarkably, it is clear that the neuronal damage, the intensity and stage of disease greatly condition the beneficial or detrimental use of nutraceuticals and autophagy tuning in brain injury and aging (Galluzzi et al, 2017;Yessenkyzy et al, 2020).…”

Molecular Insights Into Therapeutic Potential of Autophagy Modulation by Natural Products for Cancer Stem Cells

“…Program cell death or apoptosis is an acute cellular mechanism which facilitates survival as well as death via a multiple signaling transduction pathway (Elmore, 2007;Rahman et al, 2020b). Generally, the apoptotic pathway is damaged during cancer progression and development (Plati et al, 2011).…”