Neuroprotective effect of TNF alpha against the beta-amyloid neurotoxicity mediated by CDK5 kinase

Orellana, DI; Quintanilla, RA; Maccioni, RB

Abstract

The tumor necrosis factor alpha (TNFα) plays a dual role in producing either neurodegeneration or neuroprotection in the central nervous system. Despite that TNFα 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 Aβ treatments. Since TNFα affects cdk5 activity, we investigated its possible protective role against the Aβ-induced neurodegeneration, as mediated by cdk5. TNFα pretreatments significantly reduced the hippocampal neuronal cell death induced by the effects of Aβ42 peptide. In addition, this pretreatment reduced the increase in the activity of cdk5 induced by Aβ42 in primary neurons. Next, we investigated the Alzheimer type phosphorylation of tau protein induced by Aβ42. We observed that the pretreatment of neurons with TNFα reduces tau hyperphosphorylation. Taken together, these results define a novel neuroprotective effect of TNFα 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 Aβ peptide plays a key role in the development of Alzheimer etiopathogenesis. © 2006 Elsevier B.V. All rights reserved.

Más información

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
Volumen: 1773
Número: 2
Editorial: ELSEVIER SCIENCE BV
Fecha de publicación: 2007
Página de inicio: 254
Página final: 263
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S0167488906003223
DOI:

10.1016/j.bbamcr.2006.10.010

Notas: ISI, SCOPUS