Biswas_2025_Adv.Pharmacol.Pharm.Sci_2025_8847508

Neurodegenerative diseases (NDs) represent an increasingly important burden of disease, particularly in the aging population. The etiology of NDs like Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) is associated with progressive neuronal degeneration and a paucity of effective therapies. Accumulating evidence suggests that common and intersecting genetic and pathological pathways play a critical role in disease onset and progression, revealing new opportunities for target discovery. Here, we review promising therapeutic targets based on the convergence of genetics, molecular pathology, and cellular signaling in neurodegeneration. This narrative will focus on key proteins (amyloid-beta [Abeta], tau, and alpha-synuclein) and enzymes (acetylcholinesterase and asparagine endopeptidase [AEP]), including their pathological significance and therapeutic implications. N-Methyl-D-aspartate receptors (NMDARs) and cholinergic receptor subtypes are highlighted as important regulators of neurotoxicity, synaptic transmission, and inflammation. Emerging advances in genomics, neuroimaging, and drug delivery are poised to advance precision medicine strategies for early diagnosis and intervention. Important challenges remain, including the complexity of the blood-brain barrier (BBB), pathology heterogeneity, and the need for new biomarkers. We propose that a shift from phenotype-driven diagnoses to mechanistic, genetically informed approaches may improve treatment efficacy. Target identification, validation, and targeted delivery are critical considerations for the success of future therapeutic development. This integrated view will help to inform and improve drug discovery and personalized medicine approaches in the field of neurodegeneration.