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Dopamine deficiency is mainly caused by apoptosis of dopaminergic nerve cells in the substantia nigra of the midbrain and the striatum and is an important pathologic basis of Parkinson’s disease (PD). Recent research has shown that dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission plays a crucial role in dopaminergic nerve cell apoptosis. However, the upstream regulatory mechanism remains unclear. Our study showed that Drp1 knockdown inhibited aberrant mitochondrial fission and apoptosis. Importantly, we found that ROCK1 was activated in an MPP + -induced PD cell model and that ROCK1 knockdown and the specific ROCK1 activation inhibitor Y-27632 blocked Drp1-mediated aberrant mitochondrial fission and apoptosis of dopaminergic nerve cells by suppressing Drp1 dephosphorylation/activation. Our in vivo study confirmed that Y-27632 significantly improved symptoms in a PD mouse model by inhibiting Drp1-mediated aberrant mitochondrial fission and apoptosis. Collectively, our findings suggest an important molecular mechanism of PD pathogenesis involving ROCK1-regulated dopaminergic nerve cell apoptosis via the activation of Drp1-induced aberrant mitochondrial fission. Parkinson’s disease: Looking back identifies a new target Researchers in China have revealed how a protein molecule plays an early part in the molecular steps that can lead to Parkinson’s disease, which is caused by the death of nerve cells that make the neurotransmitter dopamine. Disruption of mitochondria, the energy-generating bodies inside cells, was already known to lead to the death of dopamine-producing cells. Rong Zhang, Guobing Li and colleagues at The Second Affiliated Hospital of Army Medical University in Chongqing, China traced the chain of cause and effect back to a protein called ROCK-1. Using a mouse model of Parkinson’s disease, they found that ROCK-1 activates another protein previously shown to trigger the disruption of mitochondria. ROCK-1’s early role in the sequence might make it a suitable target for treatment using drugs that inhibit its activity.

IR-783, a near-infrared heptamethine cyanine dye, has been reported to possess cancer targeting and anticancer effects; However, the molecular mechanism by which IR-783 exhibits anti-breast cancer activity is unclear. In the present study, the inhibitory effects of IR-783 on the proliferation and migration of breast cancer cells were investigated. Our results revealed that IR-783 inhibited MDA-MB-231 and MCF-7 cell proliferation in a dose- and time-dependent manner by inducing cell cycle arrest at the G0/G1 phase. In addition, a Transwell assay demonstrated that IR-783 treatment suppressed the migratory ability of MDA-MB-231 and MCF-7 cells. Furthermore, IR-783 treatment decreased the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 in MDA-MB-231 cells. Furthermore, IR-783 induced MDA-MB-231 and MCF-7 cell mitochondrial fission, and also decreased the levels of ATP. This was accompanied with a decrease in polymerized filamentous actin, which is the fundamental component of filopodia at the cell surface. Collectively, the results of the present study demonstrated that IR-783 inhibited the proliferation and migration of MDA-MB-231 and MCF-7 cells by inducing mitochondrial fission and subsequently decreasing ATP levels, resulting in cell cycle arrest and filopodia formation suppression. These findings suggest that IR-783 may be developed into an effective novel drug for treating breast cancer.

Aim: To confirm Cu2-xSe nanoparticles (NPs) could inhibit autophagic degradation and based on this property to develop a novel therapeutic strategy for cancer treatment. Materials & methods: Transmission electronic microscopy and confocal laser-scanning microscope were used to observe the accumulation of autophagosome. Western blot was used to investigate the expression of autophagy-associated proteins. Chemotherapeutic drug oxaliplatin was cotreatment with Cu2-xSe in vivo and in vitro to study therapeutic efficacy of autophagy caused by Cu2-xSe NPs. Results & conclusion: Cu2-xSe NPs significantly induce autophagosome accumulation in hepatocellular carcinoma cells, and they mainly inhibit the late-stage autophagy degradation through reducing lysosomal cathepsin activity. Moreover, Cu2-xSe NPs enhance the anticancer activity of oxaliplatin in vivo and in vitro through blocking autophagosome degradation.

Dopamine deficiency caused by apoptosis of the dopaminergic nerve cells in the midbrain substantia nigra is the main pathological basis of Parkinson's disease (PD). Recent research has shown that dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission plays an important role in dopaminergic nerve cell apoptosis. However, the upstream regulatory mechanism remains unclear. Our study shows that knockdown of Drp1 blocked aberrant mitochondrial fission and dopaminergic nerve cell apoptosis. Importantly, we found that ROCK1 was activated in an MPP+-induced PD cell model and that ROCK1 knockdown and the specific ROCK1 activation inhibitor Y-27632 blocked Drp1-mediated aberrant mitochondrial fission and apoptosis of dopaminergic nerve cell through suppression of Drp1 dephosphorylation/activation. Our in vivo study confirmed that Y-27632 significantly improved symptoms of a PD mouse model through inhibition of Drp1-mediated aberrant mitochondrial fission and apoptosis of dopaminergic nerve cell. Collectively, Our study suggests an important molecular mechanism of PD pathogenesis involving ROCK1-regulated dopaminergic nerve cell apoptosis via activation of Drp1-induced aberrant mitochondrial fission.