Multi Target Directed Ligand for Alzheimer’s Disease: A Review of Therapeutic Strategies and Advances

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and memory loss, resulting from various pathological processes such as amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, cholinergic dysfunction, and metal ion imbalance. Current treatments, like acetylcholinesterase inhibitors and NMDA receptor antagonists, only help with the symptoms and don't change how the disease gets worse. The fact that AD has many causes shows how important it is to come up with new ways to treat it. Multi-target directed ligands (MTDLs) have become a promising approach in the last few years. They are meant to work on several important molecular targets that are thought to play a role in the development of Alzheimer's disease. This review summarises progress in the creation and design of MTDLs. It talks about hybrid molecules (like tacrine–chromene derivatives), peptide-based scaffolds, flavonoid conjugates, dual GSK-3β/tau aggregation inhibitors, and new PDE- and AChE-targeting compounds. Compared to regular polypharmacy, MTDLs have more benefits, such as better effectiveness, less toxicity, better compliance, and better pharmacological profiles. Recent advances in medicinal chemistry and structure-based design bolster the argument for MTDLs as next-generation therapeutic candidates, notwithstanding challenges like bioavailability and blood–brain barrier penetration. Ongoing enhancement of these compounds may eventually yield disease-modifying therapies that can impede or avert the advancement of Alzheimer's disease.