Singh_2025_Int.J.Mol.Sci_26_

Neurological disorders, encompassing neurodegenerative and neuroinflammatory conditions, present significant public health and clinical challenges. Recent research has elucidated the pivotal role of various enzymes in the onset and progression of these disorders. This review explores the therapeutic potential of targeting these enzymes with natural and synthetic molecules. Key enzymes, including acetylcholinesterase, monoamine oxidase, beta-secretase, tau kinases, caspases, and cyclooxygenase-2, are implicated in diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Modulating these enzymes can alleviate symptoms, slow disease progression, or reverse pathological changes. Natural molecules derived from plants, microbes, seaweeds, and animals have long been noted for their therapeutic potential. Their ability to interact with specific enzymes with high specificity and minimal side effects makes them promising candidates for treatment. These natural agents provide a foundation for developing targeted therapies with improved safety profiles. Simultaneously, the development of synthetic chemistry has resulted in molecules designed to inhibit neurodegenerative enzymes with precision. This review examines the progress in creating small molecules, peptides, and enzyme inhibitors through sophisticated drug design techniques. It evaluates the efficacy, safety, and mechanisms of these synthetic agents, highlighting their potential for clinical application. The review offers a comprehensive overview of recent advancements in enzyme-targeted therapies for neurological disorders, covering both natural and synthetic molecules investigated in preclinical and clinical settings. It discusses the mechanisms through which these molecules exert their effects, the challenges faced in their development, and future research directions. By synthesizing current knowledge, this paper aims to illuminate the potential of enzyme-targeted interventions in managing neurological disorders, showcasing both the promise and limitations of these approaches.