Glial-neuronal interactions in basal ganglia neurodegenerative diseases:regulatory mechanisms and potential therapeutic targets

Li Minghui; Zhang Yingbi; Zhang Xiaorui; Yin Jihong; Wang Peng

doi:10.12307/2026.644

Abstract：BACKGROUND:Glial-neuronal interactions play a crucial role in maintaining central nervous system homeostasis through metabolic support,immune regulation,and synaptic pruning.Dysfunction in these interactions is closely associated with the pathological progression of basal ganglia neurodegenerative diseases. OBJECTIVE:To summarize the regulatory mechanisms and roles of glial-neuronal interactions in basal ganglia neurodegenerative diseases and to explore their potential therapeutic targets. METHODS:Relevant literature published from January 2020 to November 2024 was retrieved from the CNKI,PubMed,and Web of Science databases.Search terms included"basal ganglia,striatum,substantia nigra,globus pallidus;glial cells,astrocytes,microglia,oligodendrocytes;neurons,neurodegeneration,synaptic dysfunction;Parkinson's disease,Huntington's disease,multiple system atrophy,neurodegenerative diseases;metabolic coupling,neuroinflammation,synaptic pruning,oxidative stress,organoid model,single-cell sequencing;therapeutic targets,glial modulation,neuroprotection,blood-brain barrier,off-target effect"in Chinese and English.Based on the inclusion and exclusion criteria,113 articles were ultimately selected for review and summarization. RESULTS AND CONCLUSION:(1)Dysregulation of glial-neuronal interactions leads to metabolic imbalance,neuroinflammation,and synaptic dysfunction,thereby exacerbating the degeneration of basal ganglia neurons.(2)In Parkinson's disease,impaired glutamate transporter function in astrocytes leads to decreased glutamate clearance and triggers neuronal toxicity.(3)In multiple system atrophy,oligodendrocyte dysfunction leads to neuronal demyelination and axonal damage.(4)In Huntington's disease,microglia exacerbate neuroinflammation by mediating cytokine release via Toll-like receptor 4.(5)Therapeutic strategies targeting glial-neuronal interactions(e.g.,cannabinoid-2 receptor agonists,nucleotide-binding oligomerization structural domain-like receptor protein 3 inhibitors,etc.)have demonstrated potential in both animal experiments and clinical trials.In conclusion,glial-neuronal interactions play a significant role in the pathological progression of basal ganglia neurodegenerative diseases.Therapeutic strategies targeting this mechanism demonstrate promising potential for treating these diseases.