IL-3 Control Tau Modifications and Protects Cortical Neurons from Neurodegeneration

A.      Zambrano; C.      Otth; R.B.       Maccioni; I.I.       Concha

doi:10.2174/156720510793499011

Abstract

Interleukin-3 (IL-3) regulates the proliferation, survival and differentiation of haematopoietic cells via interaction with specific cell-surface receptors. IL-3 is expressed in several non-hematopoietic cell types. Studies have demonstrated the presence of IL-3 in the central nervous system, however, its physiological role in these cells is poorly understood. Previously we have been demonstrated that IL-3 prevents neuronal death induced by fibrillary β amyloid in these cells, by PI 3-kinase and Jak/STAT pathway activation. In this study, we demonstrated that IL-3 significantly reduced Aβ- promoted neurite degeneration and toxicity. Thus, this cytokine provides cellular protection against Aβ neurotoxicity in primary cortical neuronal cells, by modulating microtubular dynamics and prevention of tau cleavage and hyperphosphorylation. We also demonstrates that IL-3 is expressed in the “in vivo” mouse model of AD, Tg2576, which also expresses human AβPP with the Swedish mutation. In summary, these results suggest that IL-3 could play a neuroprotective role in AD.

Keywords: IL-3, neuroprotection, Tau, Tg2576, Aβ, neurodegeneration, cytokines, caspase 3.