Is TREM2 a Stretch: Implications of TREM2 Along Spinal Cord Circuits in Health, Aging, Injury, and Disease

TL;DR

This paper reviews the role of TREM2 in spinal cord circuits, exploring its impact on health, aging, injury, and disease, and its potential as a therapeutic target.

Contribution

The paper provides a novel synthesis of TREM2's role in spinal cord and peripheral nervous system functions, emphasizing its therapeutic potential.

Findings

TREM2 influences anti- or pro-inflammatory responses in a context-dependent manner in the CNS.

TREM2's role in motoneurons and sensory neurons remains underexplored but is critical for spinal cord function.

TREM2 may serve as a feasible therapeutic target for sensorimotor circuit damage.

Abstract

Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is a receptor found in microglia within the central nervous system (CNS) as well as in several other cell types throughout the body. TREM2 has been highlighted as a “double-edged sword” due to its contribution to anti- or pro-inflammatory signaling responses in a spatial, temporal, and disease-specific fashion. Many of the functions of TREM2 in relation to neurological disease have been elucidated in a variety of CNS pathologies, including neurodegenerative, traumatic, and vascular injuries, as well as autoimmune diseases. Less is known about the function of TREM2 in motoneurons and sensory neurons, whose cell bodies and axons span both the CNS and peripheral nervous system (PNS) and are exposed to a variety of TREM2-expressing cells and mechanisms. In this review, we provide a brief overview of TREM2 and then highlight the literature detailing the involvement of TREM2 along the spinal cord, peripheral nerves and muscles, and sensory, motor, and autonomic functions in health, aging, disease, and injury. We further discuss the current feasibility of TREM2 as a potential therapeutic target to ameliorate damage in the sensorimotor circuits of the spinal cord.

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