Accetta, Roberta (2011) Redox signal transduction in oligodendrocytes differentiation: implications for multiple sclerosis pathogenesis. [Tesi di dottorato] (Unpublished)
Restricted to Repository staff only until 30 January 2015.
MS is a chronic demyelinating disease affecting OLs, responsible for axon myelination in the CNS. Remyelination, in MS lesions, is dependent on the recruitment and differentiation of OPCs. During inflammation high levels of ROS can be achieved within MS lesions changing the local environment where OPCs differentiation occurs. Moreover, in chronic MS lesions OPCs accumulate with loss of mature OLs, suggesting the existence of a differentiation block of OPCs. We investigated the effects of low and high ROS levels, on signaling pathways involved and the role of the main source of ROS, NADPH-oxidase (NOX) enzymes, in OPCs differentiation. We also tested the hypothesis of the presence of autoantibodies impairing OPCs differentiation in CSF or in serum of MS patients. Our results demonstrated that OPCs, exposed to mild oxidative-stress, increase expression of OLs differentiation markers; thus ROS mediate the signals leading to OPCs differentiation. Fine tuning of the type and the levels of ROS generated by NOX–PKC signals may have profound effects on OPCs differentiation. Thus, large amounts of ROS induce death of OPCs. This finding is relevant for the pathogenesis of MS lesions: whereas low ROS in limited inflammation may represent a positive re-myelination stimulus, excess of ROS produced by extensive inflammation may reduce the pool the OLs precursors and worsen MS lesions. In addiction, our data indicate that CSF and autoantibodies present in the IgG fraction from serum of MS patients inhibit OLs differentiation thus impairing myelination in CNS.
|Item Type:||Tesi di dottorato|
|Uncontrolled Keywords:||Multiple Sclerosis; Redox signal transduction; Oligodendrocytes|
|Depositing User:||Anna Tafuto|
|Date Deposited:||13 Dec 2011 11:29|
|Last Modified:||30 Apr 2014 19:48|
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