ARNT2, a transcription factor for brain neuron survival?

The processes responsible for the limited ability to divide and long surviv al of neurons are not well understood but may involve aryl hydrocarbon rece ptor nuclear translocator 2 (ARNT2), a recently identified protein, apparen tly belonging to the basic helix-loop-helix superfamily of transcription fa ctors, which is expressed almost exclusively in brain during the whole life time. In agreement, we show, in the rat, that ARNT2 immunoreactivity could be observed only within nuclei of brain neurons and of dividing and neurona l PC12 cells, a localization consistent with a role in transcription regula tion. Cell death elicited either by focal ischaemia in brain or oxidative s tress in PC12 cells was largely preceded by an almost complete suppression of ARNT2 expression. In contrast, when PC12 cell cycle progression was impa ired, ARNT2 expression was enhanced. Finally, the downregulation of ARNT2 l evels induced by antisense oligonucleotides prevented PC12 cell proliferati on and induced apoptosis. These observations support the hypothesis that AR NT2 is a neuronal transcription factor, regulating cell cycle progression a nd preventing cell death, whose sustained expression might ensure brain neu ron survival.