Three SNPs linked to MS pathology-associated genes showed a significant association with either proportion of active lesions (rs3130253/MOG), incidence of cortical gray matter lesions (rs1064395/NCAN) or the proportion of remyelinated lesions (rs5742909/CTLA4).
Both neuroprotective effects and negative effects of SIRT1 activators, SIRT1 inhibitors and SIRT2 activators are discussed in a range of different disease models, including in vitro and in vivo Alzheimer's disease (AD), Parkinson's disease (PD), Huntingdon's disease (HD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS).
Expression of sphingosine/sphingosine 1-phosphate (SPH/S1P) in resident cells of the central nervous system plays an important role in the pathogenesis of multiple sclerosis (MS).
Three SNPs linked to MS clinical severity showed a significant association between the genotype and either the proportion of active lesions (rs2234978/FAS and rs11957313/KCNIP1) or the proportion of mixed active/inactive lesions (rs8056098/CLEC16A).
FTY720/fingolimod, a prodrug for the treatment of multiple sclerosis, is phosphorylated in vivo to its active phosphorylated form by sphingosine kinase 2 and has been shown to interfere with the actions of S1P and to inhibit ceramide biosynthesis.
Genetic polymorphism (rs1800693) of TNFRSF1A (type 1 tumour necrosis factor receptor) encodes a potentially anti-inflammatory soluble truncated form of the p55 receptor, which is associated with predisposition to multiple sclerosis but protection against ankylosing spondylitis (AS).
GPR17, GPR30, GPR37, GPR40, GPR50, GPR54, GPR56, GPR65, GPR68, GPR75, GPR84, GPR97, GPR109, GPR124, and GPR126 are orphan GPCRs that have been reported with considerable effects in the prevention and/or treatment of MS in preclinical studies.
The results clearly show that mRNA expression for all three GPx4 isoforms (cytoplasmic, mitochondrial and nuclear) decline in multiple sclerosis gray matter and in the spinal cord of MOG<sub>35-55</sub> peptide-induced EAE.
Except for ADGRG1/GPR56, expression of homeostatic genes, such as P2RY12 and TMEM119, is unaltered in normal-appearing MS tissue, demonstrating overall preservation of microglia homeostatic functions in the initiation phase of MS.
TRPM7 was found to be highly expressed in reactive astrocytes within well-characterized MS lesions and upregulated in primary astrocytes under chronic inflammatory conditions.
Here, we demonstrate that angiopoietin-like 4 (ANGPTL4), a potent inhibitor of LPL, is abundantly expressed in astrocytes in control white matter tissue and its expression is markedly reduced in active MS lesions.
In particular, oligodendroglial-specific MCT8 deficiency may restrict the intracellular T<sub>3</sub> availability, culminating in deficient metabolic communication between the oligodendrocytes and the neurons they ensheath, potentially promulgating neurodegenerative adult diseases such as multiple sclerosis (MS).
CC, syntaxin rs1569061 1A gene for 33-bp promoter region TC haplotypes, and synaptotagmin XI gene were found to be associated with an increased risk for multiple sclerosis (p=0.012).
Here, we report that the microtubule-associated protein (MAP) Tau exerts a gender-specific protective function on disease progression in the MS model experimental autoimmune encephalomyelitis (EAE).
The percentage of cells that expressed BMPs, BMPRII, and pSMAD1/5/8 correlated with the inflammatory activity of MS lesions, and changes in the percentage of positive cells were more relevant in MS than in other white matter-damaging diseases.
Our data suggest that increased NOX5 expression and decreased levels of NOX4 might be related with oxidative stress related vascular changes in MS patients.
These findings suggest that AGO2 and CSTF2 can be considered as potential theoretical biomarkers for MS and can be helpful for diagnosis and prognosis of responding patients to interferon.