Natural Chiral Scaffolds in Alzheimer's Disease: Therapeutic Potential, Mechanism, and Clinical Aspects

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive impairment, amyloid-β deposition, tau pathology, oxidative stress, neuroinflammation, and dysfunction of synapses. Current therapeutic options are largely symptomatic and lack disease-modifying efficacy. Target binding, pharmacokinetics, and therapeutic efficacy in AD are all significantly impacted by the stereochemistry of many bioactive natural scaffolds, which are enantiomerically defined molecules. Due to the complexity of their stereochemical structures and their multiple-target pharmacological attributes, natural chiral scaffolds have received significant attention as lead compounds to treat AD. The chirality has a critical impact on target selectivity, receptor binding, blood-brain barrier permeability, and pharmacokinetic behavior. By combining stereochemistry with pharmacological and clinical data, it is possible to expedite the discovery of safer and more effective disease-modifying therapies, thus making chiral natural products attractive for AD drug discovery in the future.