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Review
. 2023 Jul 31;13(8):1196.
doi: 10.3390/biom13081196.

Polyphenols, Autophagy and Neurodegenerative Diseases: A Review

Vichitra Chandrasekaran  1   2 , Tousif Ahmed Hediyal  1   2 , Nikhilesh Anand  3 , Pavan Heggadadevanakote Kendaganna  2 , Vasavi Rakesh Gorantla  4 , Arehally M Mahalakshmi  1   2 , Ruchika Kaul Ghanekar  5 , Jian Yang  6 , Meena Kishore Sakharkar  6 , Saravana Babu Chidambaram  1   2
Affiliations
Review

Polyphenols, Autophagy and Neurodegenerative Diseases: A Review

Vichitra Chandrasekaran et al. Biomolecules. .

Abstract

Polyphenols are secondary metabolites from plant origin and are shown to possess a wide range of therapeutic benefits. They are also reported as regulators of autophagy, inflammation and neurodegeneration. The autophagy pathway is vital in degrading outdated organelles, proteins and other cellular wastes. The dysregulation of autophagy causes proteinopathies, mitochondrial dysfunction and neuroinflammation thereby contributing to neurodegeneration. Evidence reveals that polyphenols improve autophagy by clearing misfolded proteins in the neurons, suppress neuroinflammation and oxidative stress and also protect from neurodegeneration. This review is an attempt to summarize the mechanism of action of polyphenols in modulating autophagy and their involvement in pathways such as mTOR, AMPK, SIRT-1 and ERK. It is evident that polyphenols cause an increase in the levels of autophagic proteins such as beclin-1, microtubule-associated protein light chain (LC3 I and II), sirtuin 1 (SIRT1), etc. Although it is apparent that polyphenols regulate autophagy, the exact interaction of polyphenols with autophagy markers is not known. These data require further research and will be beneficial in supporting polyphenol supplementation as a potential alternative treatment for regulating autophagy in neurodegenerative diseases.

Keywords: autophagy; neurodegenerative diseases; neuroinflammation; polyphenols; proteinopathies.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pharmacokinetic profile of curcumin. Comparison of the pharmacokinetic profile of curcumin, nanocurcumin and marketed curcumin capsules. The figure is reused as per the journal’s copyright permission [26].
Figure 2
Figure 2
Pharmacokinetic profile of berberine. Comparison of pharmacokinetic profile of berberine and berberine nanoparticles. The figure is reused as per the journal’s copyright permission [27].
Figure 3
Figure 3
Autophagy dysregulation in different neurodegenerative diseases. Different stages of autophagy are affected in neurodegenerative diseases. Parkinson’s disease (PD)—the cargo initiation step, Alzheimer’s disease (AD)—initiation of autophagosome, Huntington’s disease (HD)—formation of autophagosome, amyotrophic lateral sclerosis—autolysosome formation is inhibited. These ultimately lead to cognitive impairment.
Figure 4
Figure 4
Regulation of autophagy by polyphenol supplementation in neurodegenerative diseases. Polyphenol supplementation regulates autophagy and aids in the clearance of misfolded proteins by entering cytoplasm. Polyphenols inhibit the PI3K/AKT pathway and thereby activate the AMPK and SIRT1 pathways and inhibit the mTOR pathway. Furthermore, they activate the ULK1/2 complex, which initiates the autophagy process by increasing the levels of beclin1 and LC3 proteins.
See this image and copyright information in PMC

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