Role of TREM2 in neuroinflammation

Altaf A Abdulkhaliq; Glowi Alasiri; Yousef Almoghrabi; Bonglee Kim; Johra Khan; Amir Ajoolabady; Jun Ren; Jaakko Tuomilehto; Anwar Borai; Domenico Pratico

doi:10.1016/j.expneurol.2025.115547

Role of TREM2 in neuroinflammation

Exp Neurol. 2026 Feb:396:115547. doi: 10.1016/j.expneurol.2025.115547. Epub 2025 Nov 8.

Authors

Affiliations

¹ Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia.
² Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia.
³ Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Regenerative Medicine Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Department of Pathology, College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemun-gu, Seoul 02447, Republic of Korea.
⁵ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia.
⁶ National Clinical Research Center for Interventional Medicine, Shanghai 200032, China; State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁷ National Clinical Research Center for Interventional Medicine, Shanghai 200032, China; State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai, China.
⁸ Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
⁹ King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia.
¹⁰ Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA. Electronic address: praticod@temple.edu.

PMID: 41213496
DOI: 10.1016/j.expneurol.2025.115547

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) is cell surface transmembrane receptor of the TREM family, predominantly expressed on microglia within the central nervous system (CNS). Accumulating evidence has highlighted a critical role for microglial TREM2 in modulating inflammatory signaling pathways, thereby influencing the course of neuroinflammation - a central pathological hallmark of various neurodegenerative and CNS disorders. In this review, we aim to elucidate the molecular mechanisms by which TREM2 regulates neuroinflammatory processes, with a particular focus on the most recent advances in the field. A deeper understanding of TREM2-mediated signaling may uncover novel therapeutic targets and pathways with significant translational potential for treatment of CNS diseases.

Keywords: Alzheimer's and Parkinson's diseases; Brain hemorrhage; Microglia; Neurodegenerative diseases; Neuroinflammation; TREM2.

Publication types

Review

MeSH terms

Animals
Humans
Membrane Glycoproteins* / metabolism
Microglia / metabolism
Neuroinflammatory Diseases* / metabolism
Neuroinflammatory Diseases* / pathology
Receptors, Immunologic* / metabolism
Signal Transduction / physiology

Substances

Receptors, Immunologic
Membrane Glycoproteins
TREM2 protein, human