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
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
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.