TY - JOUR
T1 - Soluble TREM2
T2 - Innocent bystander or active player in neurological diseases?
AU - Filipello, Fabia
AU - Goldsbury, Claire
AU - You, Shih Feng
AU - Locca, Alberto
AU - Karch, Celeste M.
AU - Piccio, Laura
N1 - Publisher Copyright:
© 2022
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Microglia
KW - Neurodegeneration
KW - Neuroinflammation
KW - TREM2
UR - http://www.scopus.com/inward/record.url?scp=85123089655&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2022.105630
DO - 10.1016/j.nbd.2022.105630
M3 - Review article
C2 - 35041990
AN - SCOPUS:85123089655
SN - 0969-9961
VL - 165
JO - Neurobiology of Disease
JF - Neurobiology of Disease
M1 - 105630
ER -