跳转至内容
Merck
  • Boosting the peripheral immune response in the skeletal muscles improved motor function in ALS transgenic mice.

Boosting the peripheral immune response in the skeletal muscles improved motor function in ALS transgenic mice.

Molecular therapy : the journal of the American Society of Gene Therapy (2022-04-29)
Maria Chiara Trolese, Carlotta Scarpa, Valentina Melfi, Paola Fabbrizio, Francesca Sironi, Martina Rossi, Caterina Bendotti, Giovanni Nardo
摘要

Monocyte chemoattractant protein-1 (MCP1) is one of the most powerful pro-inflammatory chemokines. However, its signaling is pivotal in driving injured axon and muscle regeneration. We previously reported that MCP1 is more strongly upregulated in the nervous system of slow-progressing than fast-progressing SOD1G93A mice, the latter showing a poor immune response and eventual massive nerve and muscle degeneration. To assess the MCP1-mediated therapeutic role, we boosted the chemokine along the motor unit of the two SOD1G93A models through a single intramuscular injection of a scAAV9 vector engineered with the Mcp1 gene. We provided direct evidence underlying the pivotal role of the immune response in driving skeletal muscle regeneration and thus the speed of ALS progression. The comparative study performed in fast- and slow-progressing SOD1G93A mice spotlights the nature and temporal activation of the inflammatory response as limiting factors to preserve the periphery and interfere with the disease course. In addition, we recorded a novel pleiotropic role of MCP1 in promoting peripheral axon regeneration and modulating neuroinflammation, ultimately preventing neurodegeneration. Altogether, these observations highlight the immune response as a key determinant for disease variability and proffer a reasonable explanation for the failure of systemic immunomodulatory treatments, suggesting new potential strategies to hamper ALS progression.

材料
货号
品牌
产品描述

Sigma-Aldrich
抗胆碱乙酰基转移酶抗体, Chemicon®, from goat
Sigma-Aldrich
抗-神经丝200 兔抗, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
抗肌动蛋白抗体,克隆C4, ascites fluid, clone C4, Chemicon®
Sigma-Aldrich
抗神经胶质纤维酸性蛋白抗体,克隆GA5, clone GA5, Chemicon®, from mouse
Sigma-Aldrich
抗GAPDH小鼠mAb(6C5), liquid, clone 6C5, Calbiochem®
Sigma-Aldrich
单克隆抗-S100B 小鼠抗, Prestige Antibodies® Powered by Atlas Antibodies, clone CL2720, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-Sirt1 antibody, Mouse monoclonal, clone SIR11, purified from hybridoma cell culture