Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer's, Parkinson's, and ALS

Abstract

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression and limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, and genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene in these once-intractable conditions. This review synthesizes the latest insights into the underlying molecular dynamics of neurodegeneration, revealing how intertwined pathways drive the course of these diseases. With an eye on the most promising advances, we explore innovative therapies emerging from cutting-edge research: nanotechnology-based drug delivery systems capable of navigating the blood-brain barrier, gene-editing tools like CRISPR designed to correct harmful genetic variants, and stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored therapies that align with individual genetic profiles, while molecular diagnostics and biomarkers are ushering in an era of early, precise disease detection. Furthermore, novel perspectives on the gut-brain axis are sparking interest as mounting evidence suggests that microbiome modulation may play a role in reducing neuroinflammatory responses linked to neurodegenerative progression. Taken together, these advances signal a shift toward a comprehensive, personalized approach that could transform neurodegenerative care. By integrating molecular insights and innovative therapeutic techniques, this review offers a forward-looking perspective on a future where treatments aim not just to manage symptoms but to fundamentally alter disease progression, presenting renewed hope for improved patient outcomes.

Keywords: Alzheimer’s disease (AD); Huntington’s disease (HD); Parkinson’s disease (PD); gene therapy; mitochondrial dysfunction; neuroinflammation; pharmacogenomics; precision medicine; protein misfolding.

Figure 1

Amyloid accumulation in Alzheimer’s disease. This figure illustrates the process of amyloid-beta (Aβ) peptide formation and accumulation, a hallmark of Alzheimer’s disease pathology. Targeting Aβ oligomers is significant because these smaller aggregates are more neurotoxic than amyloid plaques. Aβ oligomers disrupt synaptic function, impair ion homeostasis, and activate detrimental signaling pathways, making them a critical focus for therapeutic interventions aimed at halting disease progression.

Figure 2

Macrophage polarization and anti-inflammatory response.