Mechanism of PGC-1α-mediated mitochondrial biogenesis in cerebral ischemia–reperfusion injury

Abstract

Cerebral ischemia–reperfusion injury (CIRI) is a series of cascade reactions that occur after blood flow recanalization in the ischemic zone in patients with cerebral infarction, causing an imbalance in intracellular homeostasis through multiple pathologies such as increased oxygen free radicals, inflammatory response, calcium overload, and impaired energy metabolism, leading to mitochondrial dysfunction and ultimately apoptosis. Rescue of reversibly damaged neurons in the ischemic hemispheric zone is the key to saving brain infarction and reducing neurological deficits. Complex and active neurological functions are highly dependent on an adequate energy supply from mitochondria. Mitochondrial biogenesis (MB), a process that generates new functional mitochondria and restores normal mitochondrial function by replacing damaged mitochondria, is a major mechanism for maintaining intra-mitochondrial homeostasis and is involved in mitochondrial quality control to ameliorate mitochondrial dysfunction and thus protects against CIRI. The main regulator of MB is peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), which improves mitochondrial function to protect against CIRI by activating its downstream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) to promote mitochondrial genome replication and transcription. This paper provides a theoretical reference for the treatment of neurological impairment caused by CIRI by discussing the mechanisms of mitochondrial biogenesis during cerebral ischemia–reperfusion injury.

A study on the mechanism of Beclin-1 m6A modification mediated by catalpol in protection against neuronal injury and autophagy following cerebral ischemia

“…Upregulated NRF1 is associated with ameliorated depressive-like behaviors and improved cognitive dysfunctions in electroacupuncture-treated mice with post-stroke depression (Xia et al 2017 ). Molecularly, the main regulator of mitochondrial biogenesis PGC-1α improved mitochondrial function by activating its downstream genes NRF1 and TFAM, thereby remitting cerebral ischemia–reperfusion injury (Yuan et al 2023 ). More importantly, compelling evidence elicited that CAT enhanced mitochondrial biogenesis, evidenced by elevations in the expression of PGC-1α, NRF1, and TFAM (Xu et al 2020 ).…”

Overexpression of olfactory receptor 78 ameliorates brain injury in cerebral ischaemia–reperfusion rats by activating Prkaca‐mediated cAMP/PKA‐MAPK pathway

“… 2 , 5 Calcium overload plays a crucial role in the process of CIRI and triggers ischemic cascade reactions, which leads to irreversible neuronal damage. 53 , 54 Previous studies have shown that the occurrence of neurological diseases is related to intracellular calcium homeostasis disorders. 50 , 55 PKA plays a crucial role in the calcium signalling pathway of neurological diseases, and the activation of cAMP/PKA signalling pathway in the striatum is highly correlated with the loss of dopaminergic neurons in PD rats.…”

HSP90β regulates EAAT2 expression and participates in ischemia‑reperfusion injury in rats

“…There is currently a lack of effective treatment methods for ischemic stroke, an effective approach after cerebrovascular embolism in clinical practice is timely thrombolysis or endovascular intervention, intended to restore blood perfusion in the ischemic area; yet at the same time it can induce ischemia-reperfusion injury, which leads to brain damage both in the ischemic core and penumbra area. an ischemic stroke consists of two related pathological injury processes: Primary ischemia-induced brain injury and secondary ischemia reperfusion injury (3). a study has shown that neurons in the ischemic penumbra may undergo apoptosis hours or days after ischemia and alleviating ischemia reperfusion injury is an achievable therapeutic goal in the early intervention of ischemic stroke aimed at limiting the amount of infarction (4).…”