Regulation of myocyte enhancer factor-2 transcription factors by neurotoxins

Various isoforms of myocyte enhancer factor-2 (MEF2) constitute a group of nuclear proteins found to play important roles in increasing types of cells. In neurons, MEF2s are required to regulate neuronal development, synaptic plasticity, as well as survival. MEF2s promote the survival of several types of neurons under different conditions. In cellular models, negative regulation of MEF2s by stress and toxic signals contributes to neuronal death. In contrast, enhancing MEF2 activity not only protects cultured primary neurons from death in vitro but also attenuates the loss of dopaminergic neurons in substantia nigra pars compacta in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. In this work, the mechanisms of regulation of MEF2 function by several well-known neurotoxins and their implications in various neurodegenerative diseases are reviewed.

► MEF2s are required to regulate neuronal development, synaptic plasticity, as well as survival. ► Negative regulation of MEF2s by stress and toxic signals contributes to neuronal death. ► Enhancing MEF2 activity protects neurons from death induced by neurotoxins. ► Deregulation of MEF2 function by several well-known neurotoxins implicates loss of MEF2 activity in various neurodegenerative diseases.