Acta Neuropathologica: In the MS model, TREM2 activation on small glial cells promotes myelin fragment removal and myelin re-formation.

Multiple sclerosis (MS) is a chronic demyelinative disease of the central nervous system (CNS) that involves inflammation and neurodegenerative lesions.
current MS immunomodulation therapy targets inflammation of the central nervous system, but there is still a lack of treatments that can regenerate myelin and stop the progress of the disease.
less protrusion glial precellular cells (OPCs) are multi-energy progenitor cells widely distributed in the central nervous system and can be differentiated into mature less protrusion glial cells (OLs) to maintain re-myelinization.
in MS, OLs damage caused by OPC can lead to persistent demyelination, myelin fragmentation, and axon damage, which is clinically manifested as neurological dysfunction.
effective removal of myelin fragments and removal of phagocytostic cells is key to eliminating inhibitory signal interference with OPC activation, recruiting demyelination and/or differentiation into mature OLs with myelin.
small glial cells are essential for removing myelin fragments from the demyelination region, which is a key step towards re-myelinization.
TREM2 is expressed by small glial cells and promotes the survival, proliferation and phagocytostic activity of small glial cells.
in this paper, we demonstrate that TREM2 is highly expressed in myelin-rich phagocytosis in active demyelination of the central nervous system in MS patients.
in gene expression studies, macrophages in patients with TREM2 gene defects showed a defect in the phagocytopathy.
treatment with a new TREM2 exciter antibody promotes the removal of myelin fragments in cnS demyelination models, including by facilitating the absorption and degradation of myelin, thereby accelerating the removal of myelin fragments by small glial cells.
Most importantly, TREM2 activation, which relies on antibodies on small glial cells, increases the density of less protrusive glial cell prescells in the demyelination region and the formation of mature less protrusive glial cells, thereby enhancing myelin regeneration and axon integrity.
these results are relevant because they suggest treM2 is a potential new target for small glial cells, thereby promoting re-myelinization.
: The 6-8-week-old Trem2 plus/- mice were given AL002a intravenously.
48 hours after the injection, the brain is removed after fusion with PBS, microsection is performed to separate the pineal body (CC) and the cortical layer (Ctx) and immediately freeze in liquid nitrogen.
dissolves tissue in the N-Per lysate buffer (87792, ThermoFisher) and uses the Pierce-Bicinonic acid (BCA) protein analysis kit (23227, Thermo-Scientific) to measure cell protein content.
used the mouse Trem-2b/Fc chimline (R-amp;D system) as a capture antibody and was wrapped overnight on a 96-well Meso-Scale (Discovery MSD) board in PBS at 4 degrees C.
, seal the hole 1h at 37 degrees C with a binding buffer (3% BSA in PBS).
samples and standards are titred at room temperature (RT) and cultured at 500 rpm on a vibratory sieve at 1 h.
for testing, (0.5mg/ml) sulfonyl-labeled goat anti-rat IgG (MSD) was added to the tablet.
cleaning, add a read buffer and read the board on the fan-forming camera.
wash in PBS three times between steps with 0.05% Tween 20.
antibody content is standardized to serum and protein content.
All in all, our research shows that TREM2 targeted therapy strategies for small and medium glial cells in CNS are feasible and may be a promising MS intervention to facilitate the removal of myelin fragments by small glial cells, facilitate the recruitment of OPCs, and their subsequent differentiation into mature myelin to produce less protrusive glial cells, ultimately leading to regenerative myelin and axon protection.
Cignarella, F., Filipello, F., Bollman, B. et al. TREM2 activation on microglia promotes myelins debris clearance and remyelination in a model of multiple sclerosis. Acta Neuropathol 140, 513-534 (2020). MedSci Original Source: MedSci Original Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Originals" are owned by Mets Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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