Microglia in the crosstalk between peripheral and central nervous systems in Parkinson's disease

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Parkinson's disease (PD) is increasingly recognized as a multisystem disorder involving pathological α-synuclein (α-syn) accumulation and widespread neuroimmune dysregulation. Microglia, the resident immune cells in the central nervous system (CNS), are pivotal mediators of the bidirectional communication between the CNS and peripheral systems. In addition to sensing neuronal injury and α-syn pathology, microglia dynamically respond to peripheral immune signals, including circulating cytokines, immune cell infiltration, and microbial metabolites, through pattern recognition receptors such as Toll-like and NOD-like receptors. Furthermore, microglia regulate blood-brain barrier integrity, modulate peripheral immune cell recruitment, interact with meningeal lymphatic vessels, and contribute to the propagation of α-syn within the CNS and along the gut-brain axis. However, a comprehensive framework encompassing their diverse roles in peripheral-central immune crosstalk remains underdeveloped. This review synthesizes recent advances elucidating how microglia link the CNS to peripheral immune and metabolic signals in PD. We further highlight microglial contributions to α-syn propagation along the gut-brain axis and discuss how their functional states influence disease progression. A deeper understanding of microglial involvement in this complex neuroimmune interface may inform the dev

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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