Guardians of homeostasis: Natural products target metabolic reprogramming in Alzheimer's disease

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder, defined pathologically by the accumulation of Aβ plaques and Tau neurofibrillary tangles, accompanied by widespread metabolic dysregulation. Recently, "metabolic reprogramming (MetR)", referring to the dynamic adaptation of cellular metabolic networks in response to environmental or functional demands, has emerged as a novel conceptual perspective for understanding AD. In the context of AD, the dysregulation of MetR is manifested by widespread disturbances in glucose, lipid, and amino acid metabolism, in addition to mitochondrial impairment. The distinctive therapeutic potential of natural products (NPs) in the management of AD is highlighted by their ability to act synergistically to rebalance disrupted metabolic pathways, owing to their multitarget actions, low toxicity, and broad bioactivity. This review provides a comprehensive overview of the pathological characteristics and molecular basis of "metabolic-mitochondrial" reprogramming in AD and focuses on the potential mechanisms of NPs in this context. Elucidation of these mechanisms is expected to provide novel theoretical foundations and strategic directions for early diagnosis, targeted intervention, and the pharmacological development of NPs-based therapies for AD.