Structural fingerprinting of pleiotropic flavonoids for multifaceted Alzheimer's disease

Alzheimer's disease has emerged as one of the most challenging neurodegenerative diseases associated with dementia, loss of cognitive functioning and memory impairment. Despite enormous efforts to identify disease modifying technologies, the repertoire of currently approved drugs consists of a few symptomatic candidates that are not capable of halting disease progression. Moreover, these single mechanism drugs target only a small part of the pathological cascade and do not address most of the etiological basis of the disease. Development of therapies that are able to simultaneously tackle all the multiple interlinked causative factors such as amyloid protein aggregation, tau hyperphosphorylation, cholinergic deficit, oxidative stress, metal dyshomeostasis and neuro-inflammation has become the focus of intensive research in this domain. Flavonoids are natural phytochemicals that have demonstrated immense potential as medicinal agents due to their multiple beneficial therapeutic effects. The polypharmacological profile of flavonoids aligns well with the multifactorial pathological landscape of Alzheimer's disease, making them promising candidates to overcome the challenges of this neurodegenerative disorder. This review presents a detailed overview of the pleiotropic biology of flavonoids favourable for Alzheimer therapeutics and the structural basis for these effects. Structure activity trends for several flavonoid classes such as flavones, flavonols, flavanones, isoflavones, flavanols and anthocyanins are comprehensively analyzed in detail and presented.