Alonge Paolo, Balistreri Carmela Rita, Torrente Angelo, Magro Daniele, Rubino Elisa, Monastero Roberto
Memory and Parkinson's Disease Center, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Via La Loggia 1, 90129 Palermo, Italy.
Cellular and Molecular Laboratory, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, 90134 Palermo, Italy.
Brain Sci. 2025 Apr 5;15(4):379. doi: 10.3390/brainsci15040379.
: The activation of microglia and the activity of innate immunity have recently been recognized as part of Parkinson's Disease (PD) pathophysiology. Triggering receptor expressed on myeloid cells 2 (TREM2) is a gene with neuroprotective roles. Its variations are associated with microglial-associated neurodegeneration. The objective of the present review is to investigate the current evidence on the role of TREM2 in PD pathophysiology. : A comprehensive search was performed using PubMed, Medline, and Web of Science, looking for English papers investigating the role of TREM2 in PD, or more in general, the genetic profile of microglia. : Thirty-one papers were considered relevant. Preclinical studies with PD models showed some contradictory results, even if a loss of function of TREM2 is generally associated with a microglial activation in α-synuclein-induced inflammatory processes. The role for TREM2 genetic variations in PD patients should be taken with even more caution. The increase in the soluble extracellular segment of TREM2 (sTREM2) in cerebrospinal fluid of PD patients seems to be associated with increased risk of cognitive decline. : There is increasing evidence that TREM2 may have an important role in PD pathophysiology as demonstrated by preclinical and clinical studies. Further investigations are needed to confirm this role and may lead the way for future targeted therapies for different neurodegenerative disorders.
小胶质细胞的激活和先天免疫活性最近被认为是帕金森病（PD）病理生理学的一部分。髓系细胞触发受体2（TREM2）是一个具有神经保护作用的基因。其变异与小胶质细胞相关的神经退行性变有关。本综述的目的是研究目前关于TREM2在PD病理生理学中作用的证据。：使用PubMed、Medline和Web of Science进行了全面检索，寻找研究TREM2在PD中的作用，或者更一般地说，小胶质细胞基因谱的英文论文。：31篇论文被认为相关。PD模型的临床前研究显示了一些相互矛盾的结果，尽管TREM2功能丧失通常与α-突触核蛋白诱导的炎症过程中的小胶质细胞激活有关。对于PD患者中TREM2基因变异的作用应更加谨慎对待。PD患者脑脊液中可溶性细胞外片段TREM2（sTREM2）的增加似乎与认知能力下降风险增加有关。：越来越多的证据表明，如临床前和临床研究所示，TREM2可能在PD病理生理学中起重要作用。需要进一步研究来证实这一作用，并可能为未来针对不同神经退行性疾病的靶向治疗指明方向。
