Critical role of Pin1 on neuronal rescue after transient ischemic brain injury

Abstract

Pin1 contains two functional domains, an N‐terminal WW domain and a C‐terminal PPIase domain. We defined a critical role of Pin1 on neuronal rescue through Pin1 inhibitor treatment after ischemic brain injury (MCAo). Juglone (Jug, 1 mg/kg), Pin1 inhibitor, was administered once a day for 7 days after MCAo. Analysis in histology, protein, and gene were used to determine neural cell death and survival pathway at day 7. MCAo+Jug group lead to significant downregulation of Bcl‐2 and Bax expression compared with MCAo+Veh group (p <.01). MCAo+Jug group was shown to reduce the levels of Pin1, Tau5, and phspho‐TauThr231 in both immunoblotting and immunostaining (p<.01). On the other hands, mature‐BDNF was significantly augmented in MCAo+Jug compared to MCAo+Veh (p<.01). These results suggest that Pin1 isomerase is not only acts to accelerate an intrinsic apoptotic pathway but also interrupt to turn on the cell survival machinery after MCAo. Finally, Pin1 inhibition might alleviate the acceleration of apoptotic cell death that switch on the neuronal cell rescue signal after focal cerebral ischemic in rats.Support or Funding InformationFunding: NRF‐2012R1A1A2005089, NRF‐2013R1A2A2A01067169