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Neuritogenesis and neuronal differentiation promoted by 2,4-dinitrophenol, a novel anti-amyloidogenic compound

Ana Paula Wasilewska-Sampaio^*, Mariana S. Silveira, Oliver Holub^*, Rejane Goecking^*, Flávia C. A. Gomes, Vivaldo Moura Neto, Rafael Linden, Sérgio T. Ferreira^*,1 and Fernanda G. De Felice^*,1

^* Instituto de Bioquímica Médica, Programa de Bioquímica e Biofísica Celular,
Instituto de Biofísica Carlos Chagas Filho, and
Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ Brazil

¹ Correspondence: E-mail: F.G.F., felice{at}bioqmed.ufrj.br or S.T.F., ferreira{at}bioqmed.ufrj.br

Neurite outgrowth is a critical event in neuronal development, formation, and remodeling of synapses, response to injury, and regeneration. We examined the effects of 2,4-dinitrophenol (DNP), a recently described blocker of the aggregation and neurotoxicity of the ß-amyloid peptide, on neurite elongation of central neurons. Morphometric analysis of rat embryo hippocampal and cortical neuronal cultures showed that neurite outgrowth was stimulated by DNP. This effect was accompanied by increases in the neuronal levels of the microtubule-associated protein tau and of cyclic adenosine 3',5' monophosphate (cAMP). DNP also promoted cAMP accumulation, increased tau level, neurite outgrowth, and neuronal differentiation in the mouse neuroblastoma cell line N2A. We show that DNP-induced differentiation requires activation of the extracellular signal-regulated kinase (ERK). The finding that DNP promotes neuritogenesis and neuronal differentiation suggests that, in addition to its anti-amyloidogenic actions, it may be a useful lead compound in the development of novel therapeutic approaches targeting neurite dystrophy and synaptic dysfunction in neurodegenerative pathologies such as Alzheimer’s disease.— Wasilewska-Sampaio, A. P., Silveira, M. S., Holub, O., Goecking, R., Gomes, F. C. A., Neto, V. M., Linden, R., Ferreira, S. T., De Felice, F. G. Neuritogenesis and neuronal differentiation promoted by 2,4-dinitrophenol, a novel anti-amyloidogenic compound.

Key Words: DNP • central neurons • cAMP • neuritogene-sis • tau • differentiation

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