CD45 Inhibits CD40L-induced Microglial Activation via Negative Regulation of the Src/p44/42 MAPK Pathway

IFN-γ receptor signaling mediates spinal microglia activation driving neuropathic pain

“…This kinase was up-regulated exclusively in microglia in a model of neuropathic pain (17) and was implicated in various cellular events in microglia (37)(38)(39)(40). Previous work using Lyndeficient mice also showed attenuated microglia activation evoked by ␤-amyloid peptide in the brain (39), supporting our notion that Lyn is critically involved in the molecular machinery underlying microglia activation.…”

Induction of gp130-related Cytokines and Activation of JAK2/STAT3 Pathway in Astrocytes Precedes Up-regulation of Glial Fibrillary Acidic Protein in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Model of Neurodegeneration

“…Although activation of ERK1/2 by MPTP appears to be unrelated to activation of STAT3, because it was blocked by nomifensine, our findings link activation of ERK1/2 to damage of the dopaminergic nerve terminal by MPTP. In agreement with these findings associated with damage caused by MPTP, the MAPK pathway has been shown to be activated in other brain injury models (58,59), where it is linked to the production of cytotoxic cytokines such as TNF-␣ (60). Indeed, we previously demonstrated that MPTP induces the expression of striatal TNF-␣ (61) with a time course consistent with that for microglial activation after MPTP (62).…”

High-Throughput Screening Platform for the Discovery of New Immunomodulator Molecules from Natural Product Extract Libraries

“…The critical role of Src in macrophage activation has prompted researchers to consider that the inhibition of Src activity may be a useful therapeutic strategy for macrophage-mediated diseases; specifically, Src has been described as a suitable therapeutic target for the treatment of NDD involving the activation of pathological microglia. 27 Taking into consideration other works highlighting the anti-inflammatory potential of natural products inhibitors of Src activity, 28 we expect that novel and safe compounds exhibiting strong immunosuppressive and anti-inflammatory properties might be discovered and might contribute to the development of innovative therapies for the treatment of macrophagemediated diseases. In addition, it has been demonstrated that certain antibiotics have potential as neurotherapeutics for treating neurological diseases such as amyotrophic lateral sclerosis, adult motor neuron disease, and ischemic injury.…”