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

Abstract

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.

Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

“…Results from the study show that compounds containing at least two aromatic structures (phenyl rings) and three hydroxyl groups linked with two to six atom linkers were effective anti-amyloid compounds (Porat et al 2006). Two other studies have also shown that the numbers of phenyl rings and hydroxyl groups, as well as their positions, on the molecules are important characteristics that determine the effectiveness of the aromatic compounds in their inhibition of A" aggregation (Lakey-Beitia et al 2014;Begum et al 2008).…”

“…Flavonoids are plant secondary metabolites and are a subclass of the naturally-occurring polyphenols. Flavonoids have long been known for their multi-faceted pharmacology, including anti-inflammatory, anti-oxidant, anti-tumorigenic, anti-cancer, antimicrobial, and anti-vascular properties (Ringman et al 2005;Lakey-Beitia et al (2014); Kang et al 2005). The diverse range of biological properties appears to stem from the ability of this class of compounds to bind to a multitude of cellular targets, and thereby regulate multiple cellular pathways (Ringman et al 2005;Ramassamy 2006).…”

“…As a subclass of polyphenols, flavonoids exhibit the same wide range of biological functions, including anti-oxidative, antiinflammatory, anti-tumorigenic, and antiamyloidogenic activities (Ramassamy 2006;Lakey-Beitia et al 2014). Recent studies have shown that larger flavonoid compounds that contain multiple chemical moieties, for example, dimers of single flavonoid structures or biflavonoids, show enhanced biological activities compared to their monomeric flavonoid counterparts (Zhang et al 2004;Wong et al 2007;Dhawan et al 2002).…”

Inhibition of Amyloid-like Fibril Formation of Trypsin by Red Wines

“…Non-flavonoids showed higher anti-aggregation activity than flavonoids. Polyphenols containing a higher number of aromatic rings, hydroxyl and keto groups and possess a high degree of planarity, have the largest inhibititory activity [18]. A structure-function relationship study suggested that the presence of at least two phenolic rings with two to six atomlong linkers, along with a minimum number of three hydroxyl groups on the aromatic rings, are essential for effi-cient inhibition exerted by polyphenols [5].…”

Assessment of Novel Curcumin Derivatives as Potent Inhibitors of Inflammation and Amyloid-β Aggregation in Alzheimer’s Disease

“…AD neuropathology is characterized by intraneuronal neurofibrillary tangles and extracellular senile plaques in the brain. Neurofibrillary tangles are composed of hyperphosphorylated tau proteins, while senile plaques originate from amyloid-β (Aβ) aggregation [1]. …”