Recent Advances in Pharmacological Targeting of Neurodegenerative Diseases

Abstract

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss, leading to irreversible cognitive and motor deficits. Despite decades of research, effective disease-modifying therapies remain elusive. However, recent pharmacological advances have opened new avenues for therapeutic intervention. This review highlights key developments, including the use of proteolysis-targeting chimeras (PROTACs) for selective protein degradation, modulation of autophagy to enhance clearance of toxic aggregates, and nanotechnology-based drug delivery systems capable of crossing the blood-brain barrier. In addition, emerging strategies such as mRNA-based therapeutics and the repurposing of antidiabetic drugs for neuroprotection show significant promise. Collectively, these innovative approaches are reshaping the landscape of neurodegenerative disease treatment, offering new hope for disease modification and improved patient outcomes. Continued preclinical and clinical research will be critical in translating these discoveries into effective therapies. Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) represent a growing global health burden with limited therapeutic options. These disorders are characterized by progressive neuronal loss and are driven by complex pathophysiological mechanisms including protein aggregation, oxidative stress, mitochondrial dysfunction, neuroinflammation, and impaired protein clearance. Recent advances in pharmacological research have led to the development of innovative disease-modifying therapies targeting these mechanisms. This review highlights key therapeutic strategies such as monoclonal antibodies targeting amyloid-beta and tau, antisense oligonucleotides for gene silencing, small molecules promoting autophagy, and nanoparticle-based drug delivery systems designed to cross the blood-brain barrier. Additionally, repurposing of existing drugs and novel approaches like PROTACs and CRISPR-Cas9 gene editing are explored. Despite these advances, challenges remain in translating preclinical success into clinical efficacy. Continued research and integration of personalized medicine approaches are essential for developing effective and sustainable treatments for neurodegenerative diseases.