PHB blocks endoplasmic reticulum stress and apoptosis induced by MPTP/ MPP+ in PD models

Ample empirical evidence suggests that mitochondrial dysfunction and endoplasmic reticulum (ER) stress play a crucial role in the pathogenesis of Parkinson?s disease (PD). Prohibitin (PHB), a mitochondrial inner-membrane protein involved in mitochondrial homeostasis and function, may be involved in the pathogenesis of PD. We investigated the functional role of PHB in mitochondrial biogenesis and ER stress in methyl-4-phenylpyridinium (MPP +)-induced in vivo and in vitro models of PD. The overexpression of PHB in SH-SY5Y cells block ed cell death and the apoptosis induced by MPP + incubation. PHB also block ed the activation of ER stress markers, including glucose-regulated protein 78, while increasing the expression of Xbox- binding protein 1 and caspase12. Moreover, the intracerebroventricular administration of the PHB overexpression vector greatly block ed motor dysfunction and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated neurodegeneration in the mouse model of PD. The production of reactive oxygen species, ER stress, and autophagic stress induced by MPTP were also significantly block ed in PD mice overexpressing PHB. Our results suggest that PHB blocks the dopaminergic-neuron depletion by preserving mitochondrial function and inhibiting ER stress. The genetic manipulation of PHB may feature potential as a treatment for PD.

Automated summary

Prohibitin (PHB) plays a crucial role in the pathogenesis of Parkinson's disease by preserving mitochondrial function and inhibiting ER stress, offering potential as a treatment approach for PD. The genetic manipulation of PHB may prevent dopaminergic-neuron depletion and block motor dysfunction in PD models.