Neuroprotective effect of TNFα against the β-amyloid neurotoxicity mediated by CDK5 kinaseReport as inadecuate




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The tumor necrosis factor alpha TNFα plays a dual role in producing either neurodegeneration or neuroprotection in the central nervoussystem. Despite that TNFα was initially described as a cell death inductor, neuroprotective effects against cell death induced by several neurotoxicinsults have been reported. Tau hyperphosphorylation and neuronal death found in Alzheimer disease is mediated by deregulation of the cdk5-p35complex induced by Aβ treatments. Since TNFα affects cdk5 activity, we investigated its possible protective role against the Aβ-inducedneurodegeneration, as mediated by cdk5. TNFα pretreatments significantly reduced the hippocampal neuronal cell death induced by the effects ofAβ42 peptide. In addition, this pretreatment reduced the increase in the activity of cdk5 induced by Aβ42 in primary neurons. Next, weinvestigated the Alzheimer type phosphorylation of tau protein induced by Aβ42. We observed that the pretreatment of neurons with TNFαreduces tau hyperphosphorylation. Taken together, these results define a novel neuroprotective effect of TNFα in preventing neuronal cell deathand cdk5-dependent tau hyperphosphorylation. This phenomenon, taken together with other previous findings, suggests that the inflammatoryresponse due to Aβ peptide plays a key role in the development of Alzheimer etiopathogenesis.



Author: Orellana, Daniel I.; - Maccioni Baraona, Ricardo; - Quintanilla, Rodrigo A.; -

Source: http://repositorio.uchile.cl/



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