ATF4: a Novel Potential Therapeutic Target for Alzheimer's Disease

Activating transcription factor 4 (ATF4) belongs to the activating transcription factor family and its expression is increased upon the stimulation of a diverse array of microenvironmental stresses. ATF4 plays a major role in the development, metabolism, and memory formation. Alzheimer's disease (AD) is a prevalent neurodegenerative disease in aged population. The dominant pathological changes in AD brain, including the neurofibrillary tangles, consist of hyperphosphorylated tau protein, senile plaques composed of β-amyloid proteins, loss of neurons in the whole brain, and dysfunction of synapses. The protein level of ATF4 is upregulated in both AD brain and AD mouse model, indicating its latent roles in the pathogenesis of this disease. In this paper, we reviewed the related literatures about the interaction of ATF4 with the different types of pathological changes in AD brain and pointed out some unsolved problems in this area. We also proposed that a fine regulation of ATF4 in separate neurons or brain regions might be benefit to the therapy of AD.