Advancements in neurodegenerative diseases: Pathogenesis and novel neurorestorative interventions

Progressive neurodegenerative diseases (NDs) that lack effective disease-modifying treatments, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), represent significant global health challenges. In recent years, key research findings have included the role of neuroinflammation driven by microglia and astrocytes, the impact of genetic mutations, and the importance of autophagy and mitochondrial quality control in maintaining neuronal health. In this review, we summarize recent advancements of the pathogenesis of NDs, the cellular and animal models that have provided valuable insights into disease mechanisms, and the development of blood-based biomarkers for early diagnosis and monitoring of disease progression. We also highlight emerging neurorestorative therapeutic strategies involving stem cell therapy, antisense oligonucleotides, and induced pluripotent stem cells. Additionally, we cover recent clinical trials of promising drugs, such as lecanemab and donanemab for AD, and tavapadon for PD. Finally, we propose future research directions, emphasizing the need for combination therapies that target multiple pathways, the development of more precise animal models, and the integration of nanotechnology for improved drug delivery across the blood–brain barrier.