@article{10.37349/en.2026.1006127,
abstract = {The circadian clock orchestrates cellular physiology by synchronizing transcriptional, metabolic, and signaling networks with the environmental light-dark cycle. Basic helix-loop-helix ARNT-like protein 1 (BMAL1), a core transcriptional regulator of circadian timing, contributes to rhythmic gene expression and is implicated in cellular responses to stress and energy demand. Emerging evidence suggests an interplay between BMAL1 and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, a central hub controlling cell survival, metabolism, and angiogenesis. In ischemic conditions, BMAL1 is associated with increased PI3K/AKT activity and downstream mTOR signaling, which may help preserve mitochondrial integrity, limit oxidative stress, and support neuronal and vascular recovery. Conversely, BMAL1 deficiency is linked to impaired AKT phosphorylation and redox imbalance, exacerbating ischemic injury. Proteomic and functional studies further suggest that BMAL1 may contribute to metabolic reprogramming through PI3K/AKT-dependent regulation of oxidative phosphorylation and antioxidant defenses. This review is based on a focused narrative evaluation of experimental and translational studies retrieved from PubMed, emphasizing circadian regulation of PI3K/AKT signaling in ischemic and vascular contexts. Collectively, these findings support the concept that BMAL1 functions as a temporal modulator of PI3K/AKT signaling, integrating circadian and metabolic cues to promote cellular resilience. Understanding this regulatory axis may offer novel therapeutic perspectives for ischemic and neurovascular disorders associated with circadian misalignment.},
author = {Beker, Mustafa C. and Hermann, Dirk M. and Kilic, Ertugrul},
doi = {10.37349/en.2026.1006127},
journal = {Exploration of Neuroscience},
elocation-id = {1006127},
title = {BMAL1-PI3K/AKT crosstalk in ischemic injury and vascular repair: a circadian framework for neurovascular resilience},
url = {https://www.explorationpub.com/Journals/en/Article/1006127},
volume = {5},
year = {2026}
}