Neuritogenesis and neuronal differentiation promoted by 2,4-dinitrophenol, a novel anti-amyloidogenic compound.
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 beta-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
Ana Paula
AP
Instituto de Bioquímica Médica, Programa de Bioquímica e Biofísica Celular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ Brazil.
Silveira
Mariana S
MS
Holub
Oliver
O
Goecking
Rejane
R
Gomes
Flávia C A
FC
Neto
Vivaldo Moura
VM
Linden
Rafael
R
Ferreira
Sérgio T
ST
De Felice
Fernanda G
FG
D019297:2,4-Dinitrophenol / Q000494:pharmacology*; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D020935:MAP Kinase Signaling System; D051379:Mice; D008856:Microscopy, Fluorescence; D016501:Neurites / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D010446:Peptide Fragments / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology; D016875:tau Proteins / Q000737:chemistry
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D016875:tau Proteins; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D019297:2,4-Dinitrophenol; D010100:Oxygen