Soluble TREM2: Innocent bystander or active player in neurological diseases?
Microglia
Neurodegeneration
Neuroinflammation
TREM2
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
09
11
2021
revised:
10
01
2022
accepted:
11
01
2022
pubmed:
19
1
2022
medline:
8
4
2022
entrez:
18
1
2022
Statut:
ppublish
Résumé
Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by macrophages and microglia in the central nervous system (CNS). TREM2 has attracted a lot of interest in the past decade for its critical role in modulating microglia functions under homeostatic conditions and in neurodegenerative diseases. Genetic variation in TREM2 is sufficient to cause Nasu-Hakola disease, a rare pre-senile dementia with bone cysts, and to increase risk for Alzheimer's disease, frontotemporal dementia, and other neurodegenerative disorders. Beyond the role played by TREM2 genetic variants in these diseases, TREM2 engagement is a key step in microglia activation in response to different types of tissue injury (e.g. β-Amyloid deposition, demyelination, apoptotic cell death) leading to enhanced microglia metabolism, phagocytosis, proliferation and survival. TREM2 also exists as a soluble form (sTREM2), generated from receptor shedding or alternative splicing, which is detectable in plasma and cerebrospinal fluid (CSF). Genetic variation, physiological conditions and disease status impact CSF sTREM2 levels. Clinical and preclinical studies suggest that targeting and/or monitoring sTREM2 could have clinical and therapeutic implications. Despite the critical role of sTREM2 in neurologic disease, its function remains poorly understood. Here, we review the current literature on sTREM2 regarding its origin, genetic variation, and possible functions as a biomarker in neurological disorders and as a potential active player in CNS diseases and target for therapies.
Identifiants
pubmed: 35041990
pii: S0969-9961(22)00021-3
doi: 10.1016/j.nbd.2022.105630
pmc: PMC10108835
mid: NIHMS1889514
pii:
doi:
Substances chimiques
Biomarkers
0
Membrane Glycoproteins
0
Receptors, Immunologic
0
TREM2 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
105630Subventions
Organisme : NIA NIH HHS
ID : R01 AG062734
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG058501
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
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