SIRT1/AMPK/PGC1α pathway in ischemic stroke: Elucidating neuroprotective strategies (Review).

The increased prevalence of stroke around the globe is a notable challenge as there are few treatments and the long‑term effects include neurological impairment. Oxidative stress, mitochondrial dysfunction and neuroinflammation are key mechanisms underlying the complex pathophysiology of stroke, yet their precise interactions remain poorly understood. Notably, the silent information regulator 2 homolog 1 (SIRT1)/AMP‑activated protein kinase (AMPK)/peroxisome proliferator‑activated receptor γ coactivator 1‑α (PGC1α) pathway contributes to the neuronal protection against stroke damage. The possible beneficial effects through modulations of this pathway are explored in the present review, in particular, how flavonoids may provide a promising solution to reducing the consequences of stroke. Over the years, there has been a focus on treatments using alternative methods, leaving behind the traditional drugs‑based approaches. These involve researching the impacts of physical activity and caloric intake and assessing the possible advantages of naturally available products. This versatile approach provides new prospects of therapeutic development. The present comprehensive review aimed to understand the complexity of SIRT1/AMPK/PGC1α pathway with the aim to identify potential multi‑target therapeutic approaches to reduce the notable effects of stroke on global health and wellbeing and offer new promise in the current management of ischemic stroke. The present review demonstrates that SIRT1/AMPK/PGC1α is a key neuroprotective target in stroke. Moreover, it reveals that flavonoids combined with exercise and caloric restriction enhance treatment, and that flavonoid nanoparticles crossing the blood‑brain barrier offer neuroprotection. Finally, the review focuses on brain PGC1α, improved delivery and trials performed to advance stroke therapy.