Abstract::
Alzheimer’s disease is a common and most chronic neurological disorder (NDs) associated with cognitive dys-function. Pathologically, Alzheimer’s disease (AD) is characterized by the presence of β-amyloid (Aβ) plaques, hyper-phosphorylated tau proteins, and neurofibrillary tangles, however, persistence oxidative-nitrative stress, endoplasmic retic-ulum stress, mitochondrial dysfunction, inflammatory cytokines, pro-apoptotic proteins along with altered neurotransmitters level are common etiological attributes in its pathogenesis. Rivastigmine, memantine, galantamine, and donepezil are FDA approved drugs for symptomatic management of AD whereas tacrine has been withdrawn because of hepatotoxic profile. These approved drugs only exert symptomatic relief and exhibit poor patient compliance. In the current scenario, the number of published evidence shows the neuroprotective potential of naturally occurring bioactive molecules via their antioxidant, anti-inflammatory, anti-apoptotic and neurotransmitter modulatory properties. Despite of their potent therapeutic implica-tions, concerns have arisen in context to their efficacy and probable clinical outcome. Thus, to overcome these glitches many heterocyclic and cyclic hydrocarbon compounds inspired by natural sources have been synthesized and showed im-proved therapeutic activity. Computational studies (molecular docking) have been used to predict the binding affinity of these natural bioactive as well as synthetic compounds derived from natural sources for the acetylcholine esterase, α/β secretase Nuclear Factor kappa-light-chain-enhancer of activated B cells(NF-kB),Nuclear factor erythroid 2-related factor 2(Nrf2) and other neurological targets. Thus, in this review, we have discussed molecular etiology of AD, focused on the pharmacotherapeutics of natural product, chemical and pharmacological aspects and multi-targeted designed ligands (MTDLs) of synthetic and semisynthetic molecules derived from the natural sources along with some important on-going clinical trials.
Counteracting role of nuclear factor erythroid 2-related factor 2 pathway in Alzheimer's disease
