Stress is defined as any deviation from homeostasis and the body’s appropriate response to it. Multiple genes coding for transcription factors respond early (within a few hours) after nerve injury, including AP1, JUN, CREB, STAT3, NF-kB, SOX11, and ATF3. These early-response genes then act in a coordinated manner to regulate later expression of effector-regeneration-promoting genes. ATF3, an ATF/CREB transcription factor, is absent or expressed at shallow levels in naive non-injured dorsal root ganglia but is quickly induced up to 30-fold after axotomy. Besides, ATF3 is rapidly induced by various cellular stresses, including nutrient deprivation, oxidative stress, and DNA damage.
The Central nervous system (CNS), including the retina, responds with unique cellular and genetic mechanisms to traumatic episodes, aiming to combat further damage by recovery processes or apoptosis of select cellular populations, to protect neighboring cells and/or the remaining tissue. A novel non-cholinergic role for AChE, was demonstrated when rats were exposed to bright light. AChE was upregulated in distal retina neuromas (photoreceptors and bipolar cells) leading to their apoptosis. In contrast, in similar experiments on mice, ATF3 was upregulated in proximal retinal neurons (amacrine cells and ganglion cells) downregulating the expression of AChE, and probably saving these neurons from apoptosis. Intriguingly, the AChE promoter contains the consensus binding site ‘‘TGACGTCA’’ for members of the CREB proteins, suggesting that AChE expression levels may be regulated by members belonging to the ATF/CREB superfamily.
This topic focuses on the role/s of ATF3 in the stress response of CNS, including the retina. As such, we strongly encourage the submission of manuscripts on research focusing on the pathways, receptors, and the effects of any stress, including ischemia, hyperglycemia, physical injury, and others, to CNS neurons in vitro or the CNS structures in vivo on the expression of ATF3 and its interactions with other stress-induced proteins that leads to apoptosis or regeneration as important participants of stress response of glia and neurons in CNS, especially in the retina.
Yung-Chih Cheng is a current employee of Pfizer. The other Topic Editors declare no other competing interests