Upregulation of Parkinson's disease-associated protein alpha-synuclein suppresses tumorigenesis via interaction with mGluR5 and gamma-synuclein in liver cancer.

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer, indicating that PD-associated proteins may mediate the development of cancer. Here, we investigated a potential role of PD-associated protein α-synuclein in regulating liver cancer progression in vivo and in vitro. We found the negative correlation of α-synuclein with metabotropic glutamate receptor 5 (mGluR5) and γ-synuclein by analyzing the data from The Cancer Genome Atlas database, liver cancer patients and hepatoma cells with overexpressed α-synuclein. Moreover, upregulated α-synuclein suppressed the growth, migration, and invasion. α-synuclein was found to associate with mGluR5 and γ-synuclein, and the truncated N-terminal of α-synuclein was essential for the interaction. Furthermore, overexpressed α-synuclein exerted the inhibitory effect on hepatoma cells through the degradation of mGluR5 and γ-synuclein via α-synuclein-dependent autophagy-lysosomal pathway (ALP). Consistently, in vivo experiments with rotenone-induced rat model of PD also confirmed that, upregulated α-synuclein in liver cancer tissues through targeting on mGluR5/α-synuclein/γ-synuclein complex inhibited tumorigenesis involving in ALP-dependent degradation of mGluR5 and γ-synuclein. These findings give an insight into an important role of PD-associated protein α-synuclein accompanied by the complex of mGluR5/α-synuclein/γ-synuclein in distant communications between PD and liver cancer, and provide a new strategy in therapeutics for the treatment of liver cancer.

The Parkinson's disease-associated protein α-synuclein inhibits hepatoma by exosome delivery.

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer. However, their relevant pathogenesis is not clear. In the present study, we investigated the potential role of exosome-delivered α-synuclein (α-syn) in the regulation between PD and liver cancer. We cultured hepatocellular carcinoma (HCC) cells with exosomes derived from conditioned medium of the PD cellular model, and injected exosomes enriched with α-syn into the striatum of a liver cancer rat model. We found that α-syn-contained exosomes from the rotenone-induced cellular model of PD suppressed the growth, migration, and invasion of HCC cells. Integrin αVß5 in exosomes from the rotenone-induced PD model was higher than that in the control, resulting in more α-syn-contained exosomes being taken up by HCC cells. Consistently, in vivo experiments with rat models also confirmed exosome-delivered α-syn inhibited liver cancer. These findings illustrate the important role of PD-associated protein α-syn inhibiting hepatoma by exosome delivery, suggesting a new mechanism underlying the link between these two diseases and therapeutics of liver cancer.

The Parallelogram Effect of Degenerative Structures Around the Apical Vertebra in Patients with Adult Degenerative Scoliosis: The Influence of Asymmetric Degeneration and Diagonal Degeneration on the Severity of Deformity.

BACKGROUND This is the first published study assessing the parallelogram effect of degenerative structures around the apical vertebra. We evaluated the effect of degenerative structures around the apical vertebra and spinopelvic parameters on the severity of ADS. MATERIAL AND METHODS We retrospectively reviewed data on 144 patients with ADS. The coronal (coronal Cobb angle, CA) and sagittal (thoracic kyphosis, TK; sagittal vertical axis, SVA; pelvic incidence, PI; lumbar lordosis, LL; sacral slope, SS; pelvic tilt, PT) parameters, lumbar multifidus muscle atrophy (LMA), and facet joint osteoarthritis (FJOA) were evaluated. Multiple linear regression was used to assess the correlations. RESULTS LL and PT were negatively correlated with CA (P<0.001), and the correlation between LL and SVA was positive (P<0.001), as was the correlation between PI and CA (P<0.001). The correlation between SS and SVA was negative (P<0.001). The correlation between CA and concave LMA at upper or lower intervertebral level of the apical vertebra was positive (P≤0.001). The convex LMA at upper and lower intervertebral levels was negatively correlated with CA (P<0.001). Convex LMA at the upper intervertebral level and concave LMA at the lower intervertebral level of the apical vertebra were negatively correlated with the SVA (P≤0.001). FJOA works similar to LMA (P<0.05). CONCLUSIONS Spinopelvic parameters are correlated with severity of ADS. The structures around the apical vertebra are very important to maintain global alignment of the spine via the parallelogram effect.