Prompt Description

Overactivation of leucine-rich repeat kinase 2 (LRRK2) is neurotoxic and genetically linked to Parkinson’s disease; however, its role in ischemic injury remains poorly defined. This study investigated whether ischemia regulates LRRK2 expression and whether ischemia-induced LRRK2 modulates brain-derived neurotrophic factor (BDNF) signaling and neurovascular integrity. Transient oxygen–glucose deprivation (tOGD), an established in vitro model of ischemia, increased LRRK2 expression in human umbilical vein endothelial cells (HUVEC) and mouse hippocampal HT-22 neuronal cells. This increase was accompanied by suppression of BDNF, TrkB–Notch signaling, endothelial network formation, neuronal marker expression, and cellular viability. Genetic silencing of LRRK2 or pharmacological inhibition with the selective LRRK2 inhibitor MLi-2 reversed these effects in both cell types. Activation of heat shock cognate protein 70 (HSC70) by salidroside reduced LRRK2 expression and restored BDNF–Notch signaling, whereas HSC70...