Resveratrol as a Potential Therapeutic Candidate for the Treatment and Management of Alzheimer's Disease.

Nady Braidy, Bat-Erdene Jugder, Anne Poljak, Tharusha Jayasena, Hussein Mansour, Seyed Mohammad Nabavi, Perminder Sachdev, Ross Grant

Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring polyphenolic compound present in over 70 different plant-derived products, including red wine, grapes, berries, chocolate and peanuts. Clinically, resveratrol demonstrates strong antioxidant, anti-inflammatory, anti-viral, and anti-cancer properties. Although resveratrol was first isolated in 1940, it was not until the last decade that it was recognised for its potential therapeutic role in reducing the risk of neurodegenerative disorders, and Alzheimer's disease (AD) in particular. AD is the leading cause of progressive dementia, in the elderly. Resveratrol has been shown to exhibit neuroprotective effects in a variety of in vitro and in vivo models of AD. Apart from its potent antioxidant and anti-inflammatory roles, evidence suggests that resveratrol also facilitates non-amyloidogenic cleavage of the amyloid precursor protein (APP), and promotes clearance of neurotoxic amyloid beta (Aβ) peptides, a critical step in preventing and slowing down AD pathology. Resveratrol also reduces damage to neuronal cells via a variety of additional mechanisms, most notably is the activation of a new class of NAD+-dependent histone deacetylases enzymes known as sirtuins. However in spite of the considerable advances in defining the mechanism of action of resveratrol, it is unlikely to be effective as monotherapy in AD due to its poor bioavailability, biotransformation, and requisite synergism with other dietary factors. This review summarizes the relevance of resveratrol in the pathophysiology of AD. It also highlights why resveratrol alone may not be an effective single therapy, and how resveratrol coupled to other compounds might yet prove an effective therapy with multiple targets.