Pseudoginsenoside F11 ameliorates the dysfunction of the autophagy-lysosomal pathway by activating calcineurin-mediated TFEB nuclear translocation in neuron during permanent cerebral ischemia.

Pseudoginsenoside F11 ameliorates the dysfunction of the autophagy-lysosomal pathway by activating calcineurin-mediated TFEB nuclear translocation in neuron during permanent cerebral ischemia. Exp Neurol. 2021 Jan 07;:113598 Authors: Fu X, Liu Y, Zhang H, Yu X, Wang X, Wu C, Yang J Abstract We have previously found that transcription factor EB (TFEB), as a master regulator of autophagy and lysosome biogenesis, provides neuroprotective effects on cerebral ischemia-induced neuronal damage by activation of autophagy-lysosomal pathway (ALP). We have also reported that Pseudoginsenoside F11 (PF11), an ocotillol-type saponin isolated from Panax quinquefolium L., significantly attenuates the ischemic injury of rats subjected to permanent middle cerebral artery occlusion (pMCAO), possibly by alleviating the autophagic/lysosomal defects. The present study aims to investigate whether the beneficial effect of PF11 on ALP dysfunction induced by permanent ischemic stroke is based on its regulation of TFEB nuclear translocation in pMCAO rats and the oxygen-glucose-deprived (OGD) primary neurons. Meanwhile, the role of calcineurin, a serine/threonine protein phosphatase, during this process in which PF11 regulated TFEB transcriptional activity was also explored. The data showed that PF11 exerted significant protective effects on pMCAO-induced injury and decreased OGD-induced neuronal death. The nuclear localization of TFEB was decreased at 24 h a...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research