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Huntington's disease (HD) is a progressive genetic neurodegenerative disease caused by an abnormal expansion of a cytosine-adenine-guanine trinucleotide repeat in the huntingtin gene. One pathological feature of HD is neuronal loss in the striatum. Despite many efforts, mechanisms underlying neuronal loss in HD striatum remain elusive. It was suggested that the mutant huntingtin protein interacts mitochondrial proteins and causes mitochondrial dysfunction in striatal neurons. However, whether axonal transport of mitochondria is altered in HD striatal neurons remains controversial. Here, we examined axonal transport of single mitochondria labelled with Mito-DsRed2 in cultured striatal neurons of zQ175 knock-in mice (a knock-in mouse model of HD). We observed decreased anterograde axonal transport of proximal mitochondria in HD striatal neurons compared with wild-type (WT) striatal neurons. Decreased anterograde transport in HD striatal neurons was prevented by overexpressing mitochondrial Rho GTPase 1 (Miro1). Our results offer a new insight into mechanisms underlying neuronal loss in the striatum in HD. • Cultured striatal neurons were mainly MSNs that are the most vulnerable neurons in HD. • Anterograde axonal transport of proximal mitochondria was altered in HD striatal neurons. • Overexpressing Miro1 prevented altered mitochondrial transport in HD striatal neurons. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the deadliest primary brain tumor that is highly resistant to current treatments. Polo-like kinase 1 (PLK1) and signal transducer and activator of transcription 3 (STAT3) are highly expressed in gliomas, especially GBM. Previous studies have shown reciprocal activation between PLK1 and STAT3 and that they regulate the same pools of MYC downstream. We have demonstrated that PLK1 and STAT3 levels are elevated in gliomas compared with those in normal brain tissues, and high expression of both PLK1 and STAT3 is associated with poor prognosis in TCGA. Moreover, there was direct or indirect reciprocal regulation between PLK1 and STAT3. Furthermore, we found that PLK1 and STAT3 can regulate the same pools of MYC downstream. Compared to monotherapy, combined treatment of glioma cells with PLK1 and STAT3 inhibitors, BI2536 and Stattic, respectively, showed lower expression of MYC, synergistic induction of cell invasion and apoptosis in vitro, and tumor inhibition in xenografts. PLK1 and STAT3 were able to directly regulate the expression of MYC and induce apoptosis of glioma cells through the regulation of MYC. These findings may help develop a therapeutic strategy for dual inhibition of PLK1 and STAT3 against the tumorigenesis of glioma. • PLK1 and STAT3 expression increased in GBM tissues. • PLK1 interacts with STAT3 in GBM. • PLK1 and STAT3 were able to directly regulate the expression of MYC. • Dual pLK1 and STAT3 inhibition promotes glioblastoma cells apoptosis via MYC. [ABSTRACT FROM AUTHOR]