Partial inhibition of proteasome activity enhances remyelination after

VIOLETA MILLET; CRISTIAN P MOIOLA; JUANA M PASQUINI,; EDUARDO F SOTO; LAURA ANDREA PASQUINI

EXPERIMENTAL NEUROLOGY

Elsevier

Año: 2009 p. 282 - 296

0014-4886

We have previously demonstrated that addition of low concentrations of lactacystin (a specific inhibitor offic inhibitor of 27 the proteasome) to oligodendroglial cell cultures containing a high percentage of precursor cells inducesthe proteasome) to oligodendroglial cell cultures containing a high percentage of precursor cells induces 28 their exit from the cell cycle and their differentiation. On the other hand, we have recently shown that thetheir exit from the cell cycle and their differentiation. On the other hand, we have recently shown that the 29 mechanism of cuprizone toxicity on oligodendroglial cells involves the recruitment of microglia and theirmechanism of cuprizone toxicity on oligodendroglial cells involves the recruitment of microglia and their 30 secretion of pro-inflammatory cytokines and in the increased production of oxidant species, which results insecretion of pro-inflammatory cytokines and in the increased production of oxidant species, which results in 31 a decrease in the activities of the mitochondrial respiratory chain. In the present paper we investigated thea decrease in the activities of the mitochondrial respiratory chain. In the present paper we investigated the 32 effect of a decrease in proteasome activity induced by the injection of lactacystin in the corpus callosum ineffect of a decrease in proteasome activity induced by the injection of lactacystin in the corpus callosum in 33 the remyelination process that normally occurs after cuprizone-induced demyelination. This treatmentthe remyelination process that normally occurs after cuprizone-induced demyelination. This treatment 34 markedly improves the remyelination process that normally occurs in cuprizone-induced demyelination. Itmarkedly improves the remyelination process that normally occurs in cuprizone-induced demyelination. It 35 also attenuates the activation of NFêB and the recruitment of microglia and astrocytes, thus helping in thealso attenuates the activation of NFêB and the recruitment of microglia and astrocytes, thus helping in the 36 recovery of the mitochondrial respiratory chain activities that are affected by cuprizone treatment.recovery of the mitochondrial respiratory chain activities that are affected by cuprizone treatment.