Neuroprotective effect of TNF alpha against the beta-amyloid neurotoxicity mediated by CDK5 kinase
The tumor necrosis factor alpha (TNFÎ±) plays a dual role in producing either neurodegeneration or neuroprotection in the central nervous system. Despite that TNFÎ± was initially described as a cell death inductor, neuroprotective effects against cell death induced by several neurotoxic insults have been reported. Tau hyperphosphorylation and neuronal death found in Alzheimer disease is mediated by deregulation of the cdk5/p35 complex induced by AÎ² treatments. Since TNFÎ± affects cdk5 activity, we investigated its possible protective role against the AÎ²-induced neurodegeneration, as mediated by cdk5. TNFÎ± pretreatments significantly reduced the hippocampal neuronal cell death induced by the effects of AÎ²42 peptide. In addition, this pretreatment reduced the increase in the activity of cdk5 induced by AÎ²42 in primary neurons. Next, we investigated the Alzheimer type phosphorylation of tau protein induced by AÎ²42. We observed that the pretreatment of neurons with TNFÎ± reduces tau hyperphosphorylation. Taken together, these results define a novel neuroprotective effect of TNFÎ± in preventing neuronal cell death and cdk5-dependent tau hyperphosphorylation. This phenomenon, taken together with other previous findings, suggests that the inflammatory response due to AÎ² peptide plays a key role in the development of Alzheimer etiopathogenesis. Â© 2006 Elsevier B.V. All rights reserved.
|Título según WOS:||Neuroprotective effect of TNF alpha against the beta-amyloid neurotoxicity mediated by CDK5 kinase|
|Título según SCOPUS:||Neuroprotective effect of TNFa against the ß-amyloid neurotoxicity mediated by CDK5 kinase|
|Título de la Revista:||BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH|
|Fecha de publicación:||2007|
|Página de inicio:||254|