4.6 Review

Polyphenols as Therapeutic Molecules in Alzheimer's Disease Through Modulating Amyloid Pathways

Journal

MOLECULAR NEUROBIOLOGY
Volume 51, Issue 2, Pages 466-479

Publisher

SPRINGER
DOI: 10.1007/s12035-014-8722-9

Keywords

Alzheimer's disease; Polyphenols; alpha-Secretase activator; beta-Secretase inhibitor; gamma-Secretase inhibitor; A beta aggregation; Amyloid fibril disaggregation; Molecular mechanisms; Structure-activity relationships

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Funding

  1. Institute for Training and Development of Human Resources of Panama (IFARHU)
  2. National Secretariat for Science, Technology, and Innovation of Panama (SENACYT)
  3. National Science System (SNI) of SENACYT

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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 A beta aggregation, and favor disruption of preformed fibrils. Finally, the role of polyphenols in modulating Alzheimer's pathology is discussed.

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