Comprehensive Review of Neurodegenerative Disorders

Neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington'sdisease and Amyotrophic Lateral Sclerosis, represent a significant and growing global healthchallenge, particularly with aging populations. This review synthesizes current understanding, tracingthe historical recognition of these conditions to the complex molecular mechanisms now known todrive neuronal loss. Key pathogenic processes discussed include protein misfolding and aggregation(e.g., amyloid-beta, tau, alpha-synuclein, mutant huntingtin), oxidative stress linked to mitochondrialdysfunction (often exacerbated by genetic factors like SOD1 mutations), chronic neuroinflammationinvolving glial activation (microglia and astrocytes), and disruptions in proteostasis, particularlyimpaired autophagy. While current treatments remain largely symptomatic, offering temporary relief(e.g., cholinesterase inhibitors/memantine for Alzheimer's disease, levodopa for Parkinson's disease),the focus is shifting towards disease-modifying strategies. This review highlights progress inimmunotherapies targeting protein aggregates (like Lecanemab /Donanemab for amyloid-beta,Prasinezumab for alpha-synuclein), gene-targeted therapies using antisense oligonucleotides(Tofersen for SOD1) and CRISPR/Cas9 systems (preclinical work on HTT and C9orf72) and stemcell approaches using induced pluripotent stem cells. Diagnostic innovations, including advancedPET imaging, fluid biomarkers (CSF Aβ/tau, blood NfL), and digital biomarkers, are improving earlydetection and monitoring. Despite these advances, significant challenges such as diseaseheterogeneity, blood-brain barrier penetration, biomarker limitations, and socioeconomic/ethicalhurdles impede clinical translation. Future directions emphasize personalized medicine, multi-targettherapies (multi-target direct ligands, combinations), repurposed drugs (Exenatide, Pridopidine),natural compounds (Curcumin, Pingchan granule), pathway modulation (mTOR inhibitors), andpreventive strategies