PINK1 regulates mitochondrial fission/fusion and neuroinflammation in -amyloid-induced Alzheimer's disease models

Disrupted mitochondrial fission/fusion balance is consistently involved in neurodegenerative diseases, including Alzheimer's disease. PTEN-induced putative kinase 1 (PINK1), a mitochondrial kinase, has been reported to prevent mitochondrial injury, oxidative stress, apoptosis, and inflammation. However, to the best of our knowledge, the contribution of PINK1 to A beta-induced mitochondrial fission/fusion has not been reported. In the present study, we showed that PINK1 deficiency promoted mitochondrial fission and fusion, aggravated mitochondrial dysfunction, and promoted neuroinflammatory cytokine factor production induced by intracerebroventricular (ICV) injection of A beta(25-35) in rats. In vitro experiments have also showed that A beta(25-35) caused more severe cell injury in PINK1-knockdown PC12 cells. These cells suffered more extensive death when exposed to proinflammatory cytokines. Lastly, we found that PINK1 overexpression significantly inhibited mitochondrial fusion, improved mitochondrial dysfunction, and reduced neuroinflammatory cytokine production induced by A beta(25-35). The current study suggests the involvement of PINK1 in A beta(25-35)-mediated mitochondrial dynamics and that PINK1 may be a potential target for therapies aimed at enhancing neuroprotection to ameliorate A beta(25-35)- induced insults.