Small molecular therapeutic targets for neurodegenerative diseases

Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis disease are characterized by progressive neuronal loss, protein aggregation, and synaptic dysfunction. These diseases share common pathological mechanisms including oxidative stress, mitochondrial impairment, chronic neuroinflammation, protein misfolding, and epigenetic dysregulation. Current therapies offer only symptomatic relief and fail to halt disease progression. Recent advances in transcriptomics and proteomics have enabled the identification of shared molecular pathways and druggable targets across multiple neurodegenerative diseases. The key targets, such as BDNF-TrkB, TREM2, SIRT1, PINK1-Parkin, GSK-3β, NLRP3, and mTOR have shown promise in preclinical models, offering opportunities for broad-spectrum therapeutic development. Importantly, blood-brain barrier disruption and neuroinflammatory crosstalk exacerbate disease pathology and hinder drug delivery. Innovative strategies involving nanocarriers, gene therapy, and epigenetic modulation are emerging to overcome these barriers. This review highlights the convergence of disease mechanisms, discusses common molecular signatures and therapeutic vulnerabilities, and explores novel small molecular interventions targeting shared pathways mainly in AD and PD. A deeper understanding of aging-associated molecular dysfunction is essential to design sustainable, disease-modifying therapeutics with cross-disease relevance.