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Neuritogenesis and neuronal differentiation promoted by 2,4‐dinitrophenol, a novel anti‐amyloidogenic compound
Author(s) -
WasilewskaSampaio Ana Paula,
Silveira Mariana S.,
Holub Oliver,
Goecking Rejane,
Gomes Flávia C. A.,
Neto Vivaldo Moura,
Linden Rafael,
Ferreira Sérgio T.,
De Felice Fernanda G.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-3812com
Subject(s) - neurite , microbiology and biotechnology , chemistry , mapk/erk pathway , neurotoxicity , cellular differentiation , neuroprotection , kinase , biology , neuroscience , biochemistry , toxicity , in vitro , organic chemistry , gene
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 β‐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. FASEB J. 19, 1627–1636 (2005)