Toward Effective Management of Neurodegenerative Diseases: Challenges and Future Directions

Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), represent a growing global health challenge characterized by progressive neuronal loss and irreversible neurological decline. This review comprehensively explores the pathogenesis of NDs, focusing on the central roles of proteinopathy (e.g., Aβ, tau, and α-synuclein aggregation), mitochondrial dysfunction, and genetic mutations. We systematically evaluate the current landscape of pharmacological management, which primarily offers symptomatic relief through mechanisms such as cholinesterase inhibition, dopamine replacement, and glutamate regulation. Furthermore, we highlight promising advances in novel therapeutic strategies, including monoclonal antibodies (e.g., Lecanemab, Donanemab), gene therapy, and stem cell-based approaches, which aim to modify disease progression by targeting underlying pathological mechanisms. Despite these innovations, significant translational challenges persist, such as the limitations of animal models and the complexity of early diagnosis. This review concludes by discussing future directions, emphasizing the potential of personalized medicine, the gut-brain axis, and emerging targets like USP30 to overcome current hurdles and achieve effective management of these devastating disorders.