E2F transcription factor 4 (E2F4)

E2F transcription factor 4 (E2F4) is a critical protein that functions as a transcriptional repressor, primarily known for its role in controlling the cell cycle by inhibiting the transition from G1 to S phase (UniProt P35222). In the context of the E2F4-regulated neuronal gene network, it acts as a master regulator in post-mitotic neurons, maintaining their quiescent state and regulating genes essential for synaptic plasticity and survival (Hsu et al., 2019, PubMed: 31412238). Research has highlighted that this network is significantly disrupted in Alzheimer's disease, where E2F4 deficiency or dysfunction leads to the aberrant re-entry of neurons into the cell cycle, ultimately resulting in apoptosis and cognitive decline (Lopez-Sanchez et al., 2022, PubMed: 35143104). Consequently, E2F4 is being investigated as a therapeutic target for neurodegeneration, with the goal of restoring the integrity of its regulated gene network. While there are currently no FDA-approved drugs specifically targeting E2F4, experimental approaches include gene therapy to overexpress functional E2F4 and the search for small molecules that can stabilize its activity or mimic its repressive functions.

Other names

E2F-4Transcription factor E2F4p107/p130-binding protein

Transcriptional modulation to restore neuronal gene network homeostasis and suppress aberrant cell cycle re-entry in post-mitotic neurons.