Go-sha-jinki-Gan Alleviates Inflammation in Neurological Disorders via p38-TNF Signaling in the Central Nervous System.

Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine. In clinical practice, GJG is effective against neuropathic pain and hypersensitivity induced by chemotherapy or diabetes. In our previous study using a chronic constriction injury mouse model, we showed that GJG inhibited microglia activation by suppressing the expression of tumor necrosis factor-α (TNF-α) and p38 mitogen-activated protein kinase (p38 MAPK) in the peripheral nervous system. To investigate whether GJG can suppress inflammation in the central nervous system (CNS) in the context of neurological disorders, we examined the effect of GJG on the activation of resident glial cells and on p38-TNF signaling in two mouse models of neurological disorders: the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. GJG administration relieved the severity of clinical EAE symptoms and MPTP-induced inflammation by decreasing the number of microglia and the production of TNF-α in the spinal cord of EAE mice and the substantia nigra of MPTP-treated mice. Accordingly, GJG suppressed the phosphorylation of p38 in glial cells of these two mouse models. We conclude that GJG attenuates inflammation of the CNS by suppressing glial cell activation, followed by a decrease in the production of TNF-α via p38-TNF signaling.

Surface plasmon resonance characterization of specific binding of polyglutamine aggregation inhibitors to the expanded polyglutamine stretch.

Proteins with an abnormally expanded polyglutamine (polyQ) stretch are prone to change their conformations, leading to their aggregation, and cause inherited neurodegenerative diseases called the polyQ diseases. Although screening for polyQ aggregation inhibitors has been extensively performed, many common false-positive hits have been identified so far. In this study, we employed surface plasmon resonance (SPR) to characterize the binding specificities and affinities of polyQ aggregation inhibitors to the expanded polyQ stretch. SPR successfully detected specific binding of polyQ binding peptide 1 (QBP1) to the expanded polyQ stretch (K(d)=5.7 microM), and non-specific binding of Congo red to polyQ proteins independent of their polyQ-length. Binding affinities of polyQ aggregation inhibitors to the expanded polyQ stretch were correlated with their inhibitory effects on polyQ aggregation. We therefore conclude that SPR is a useful technique for screening for specific polyQ aggregation inhibitors as promising therapeutic candidates for the currently untreatable polyQ diseases.