Polyphenols as therapeutic molecules in Alzheimer's disease through modulating amyloid pathways.
Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative condition. The complex pathology of this disease includes oxidative stress, metal deposition, formation of aggregates of amyloid and tau, enhanced immune responses, and disturbances in cholinesterase. Drugs targeted toward reduction of amyloidal load have been discovered, but there is no effective pharmacological treatment for combating the disease so far. Natural products have become an important avenue for drug discovery research. Polyphenols are natural products that have been shown to be effective in the modulation of the type of neurodegenerative changes seen in AD, suggesting a possible therapeutic role. The present review focuses on the chemistry of polyphenols and their role in modulating amyloid precursor protein (APP) processing. We also provide new hypotheses on how these therapeutic molecules may modulate APP processing, prevent Aβ aggregation, and favor disruption of preformed fibrils. Finally, the role of polyphenols in modulating Alzheimer's pathology is discussed.
Centre for Biodiversity and Drug Discovery, Institute for Scientific Research and High Technology Services (INDICASAT-AIP), City of Knowledge, Panama City, Republic of Panama.
Johant
J
Lakey-Beitia
Ruben
R
Berrocal
K S
KS
Rao
Armando A
AA
Durant
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D006801:Humans; D059808:Polyphenols / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D059808:Polyphenols