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The Role of MEF2 Transcription Factor Family in Neuronal Survival and Degeneration

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MDPI
DOI: 10.3390/ijms24043120

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myocyte enhancer factor 2; neuronal survival; neurodegeneration; neuropsychiatric diseases; transcription factors

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The family of myocyte enhancer factor 2 (MEF2) transcription factors plays a crucial role in neuronal development and synaptic plasticity. MEF2s are involved in regulating the growth, pruning, and survival of neurons in the developing brain. They also impact learning and memory formation by controlling the number of synapses in the hippocampus. Dysfunctions in MEF2 activity have been linked to age-dependent neuronal dysfunctions and neurodegenerative diseases.
The family of myocyte enhancer factor 2 (MEF2) transcription factors comprises four highly conserved members that play an important role in the nervous system. They appear in precisely defined time frames in the developing brain to turn on and turn off genes affecting growth, pruning and survival of neurons. MEF2s are known to dictate neuronal development, synaptic plasticity and restrict the number of synapses in the hippocampus, thus affecting learning and memory formation. In primary neurons, negative regulation of MEF2 activity by external stimuli or stress conditions is known to induce apoptosis, albeit the pro or antiapoptotic action of MEF2 depends on the neuronal maturation stage. By contrast, enhancement of MEF2 transcriptional activity protects neurons from apoptotic death both in vitro and in preclinical models of neurodegenerative diseases. A growing body of evidence places this transcription factor in the center of many neuropathologies associated with age-dependent neuronal dysfunctions or gradual but irreversible neuron loss. In this work, we discuss how the altered function of MEF2s during development and in adulthood affecting neuronal survival may be linked to neuropsychiatric disorders.

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