ApTOLL ameliorates cognitive dysfunction and brain injury in ischemic stroke by regulating the miR-335-5p/IRAK1 axis.

ApTOLL, a promising therapeutic agent, has demonstrated effectiveness in mitigating stroke-induced neurological damage in clinical settings. Despite this, the detailed molecular mechanisms by which ApTOLL impacts ischemic stroke remain inadequately understood. In the present study, we explored how ApTOLL modulates downstream microRNAs (miRNAs) to alleviate brain damage and cognitive dysfunction associated with ischemic stroke. We established a rat model of ischemic stroke. Administration of ApTOLL upregulated miR-335-5p and suppressed IRAK1 expression in the ischemic brain. ApTOLL treatment significantly reduced infarct size, diminished neuronal apoptosis, and attenuated pathological damage in the brain. Additionally, ApTOLL led to the inhibition of inflammation and oxidative damage while enhancing autophagy. Similar effects were observed when miR-335-5p was overexpressed or IRAK1 was knocked down. Conversely, the beneficial impacts of ApTOLL were negated by miR-335-5p antagomir or IRAK1 overexpression, suggesting that ApTOLL's neuroprotective effects are mediated by the miR-335-5p/IRAK1 pathway. Mechanistically, ApTOLL exerted its protective role by promoting the expression of miR-335-5p, thereby reducing IRAK1 levels, leading to amelioration of ischemic brain damage. ApTOLL effectively mitigates ischemic stroke-induced neuronal damage by modulating the miR-335-5p/IRAK1 axis. These findings reveal a novel mechanistic pathway for ApTOLL's therapeutic effects and highlight its potential as a promising treatment strategy for ischemic stroke.