RESEARCH PAPER
Glial Plasticity and Dysfunction: Mechanistic Insights and Therapeutic Opportunities in Neurodegeneration.
AI Summary
This review synthesizes recent advances in glial heterogeneity and plasticity—covering metabolic dysfunction, inflammatory polarization, glial-immune crosstalk, and extracellular vesicle signaling—and evaluates glia-focused interventions (reprogramming, senolytics, engineered EVs, metabolic…
Why It Matters
By highlighting actionable glial mechanisms that drive neuroinflammation and metabolic failure and surveying translatable interventions and delivery/biomarker challenges, the paper identifies promising, though still preclinical, avenues to target glia for disease-modifying Parkinson's therapies.
Abstract
Recent advances, including single-cell transcriptomics, lineage tracing, and in vivo imaging, have unveiled the heterogeneity, plasticity, and functional versatility of astrocytes, microglia, oligodendrocytes, and Schwann cells. These cells respond to metabolic and immune cues, participate in synaptic regulation, and provide metabolic and trophic support to neurons. Their dual roles in neuroprotection and neurodegeneration underscore the complexity of their contributions across CNS disorders. This review examines the diverse physiological and pathological roles of glia, emphasizing their involvement in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Mechanisms including metabolic dysfunction, inflammatory polarization, glial-immune crosstalk, and extracellular vesicle-mediated signaling are critically discussed. Emerging therapeutic strategies, ranging from glial reprogramming and senolytic therapies to the use of engineered extracellular vesicles and metabolic modulators, are evaluated for their potential to harness glial plasticity and mitigate disease progression. The review also outlines current challenges in translating glial biology into clinical interventions, including cellular heterogeneity, delivery barriers, and the need for specific biomarkers. A glia-centered therapeutic paradigm offers promising avenues to restore CNS homeostasis and promote regeneration in neurodegenerative diseases.
