Work

Post-onset intermittent fasting attenuates neuroinflammation and demyelination via a TRIB3–PERK–autophagy axis in an EAE model of multiple sclerosis

Year: 2025

Type: article

Abstract: Prior studies have demonstrated therapeutic benefits of intermittent fasting (IF) in experimental autoimmune encephalomyelitis (EAE), yet they have predominantly examined prophylactic protocols or implemented short-term post-induction interventions, leaving the therapeutic window undefined and the underlying mechanisms unelucidated. Here, we systematically evaluate intermittent fasting (IF) initiated at a clinically critical juncture of 10 days post-induction (EAE_postIF), which coincides with early symptom onset, demonstrating significant attenuation of disease progression, reduced neuroinflammation, and preserved myelin integrity. Mechanistically, EAE_postIF activates a TRIB3–PERK–autophagy axis in the spinal cord, evidenced by increased ATF4, CHOP, and TRIB3 expression and suppression of mTOR signaling. In TRIB3-deficient mice, the beneficial effects of IF are partially attenuated, with clinical and histological improvements reduced relative to wild-type controls yet remaining superior to untreated cohorts. These findings establish a well-defined therapeutic window for IF intervention in neuroinflammation and identify TRIB3–PERK–autophagy signaling as a critical mediator, supporting IF as a viable metabolic strategy to complement existing MS therapies.

Source: Journal of Neuroinflammation

DOI: 10.1186/s12974-025-03640-y