Phenylpropanoids and Alzheimer's disease: A potential therapeutic platform

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by progressive dementia, neuroinflammation and the accumulation of intracellular neurofibrillary tangles and extracellular plaques. The etiology of AD is unclear, but is generally attributed to four leading hypotheses: (i) abnormal folding and aggregation of amyloid-β (Aβ)/tau proteins (ii) activation of the innate immune system, (iii) mitochondrial dysfunction, and (iv) oxidative stress. To date, therapeutic strategies have largely focused on Aβ-centric targets; however, the repeated failure of clinical trials and the continued lack of a disease-modifying therapy demand novel, multifaceted approaches. Natural products are common molecular platforms in drug development; in AD, compounds from the plant phenylpropanoid metabolic pathway have yielded promising associations. Herein, we review developments in the pathogenesis of AD and the metabolism of phenylpropanoids in plants. We further discuss the role of these metabolites as relevant to the four leading mechanisms of AD pathogenesis, and observe multiple protective effects among phenylpropanoids against AD onset and progression.