Anti-Tyrosine polyclonal antibody

Recent studies have determined that gastrointestinal function contributes to the control of Parkinson's disease (PD). Gastrointestinal dysfunction results in a leaky intestinal barrier, inducing inflammation in the gut. Korean red ginseng (KRG) is widely used for the treatment of numerous afflictions, including inflammation and neurodegenerative disease. We investigated changes in the intestinal tight junctions and proinflammatory cytokines in the colon, and alpha-synuclein (aSyn) in the colon and the substantia nigra (SN) of a PD mouse model. Eight-week-old male C57BL/6 mice were intraperitoneally administered 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) once a day for 5 days, and orally given 100 mg/kg of KRG for 12 consecutive days. Alterations in the levels of occludin, zonula occludens-1 (ZO-1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in the colon, and the expressions of aSyn and tyrosine hydroxylase (TH) in the colon and the SN were evaluated. Oral administration of KRG significantly prevents the MPTP-induced motor dysfunction, and suppresses the MPTP-induced disruption of occludin and ZO-1, and suppresses the increase in TNF-alpha and IL-1 beta in the colon of mice. In addition, KRG prevents accumulation of aSyn and TH in the colon and the SN. These results suggest that KRG has the potential to prevent MPTP-induced leaky gut barrier, inflammation, and accumulation of aSyn.

Menin serves both tumor suppressor and promoter roles in a highly tumor-specific manner. In colorectal cancer, menin is over-expressed and plays a critical role in regulating transcription of SKP2, and combined treatment with a menin inhibitor and smallmolecule EGFR inhibitor (EGFRi) leads to synergistic killing of colorectal cancer cells. However, the full spectrum of menin function in colorectal cancer remains uncertain. Herein, we demonstrate that menin inhibition increases glycolysis in colorectal cancer cells. This menin inhibitor-induced increase in glycolysis occurs in an mTOR-independent manner and enhances the sensitivity of colorectal cancer cells to EGFRis. In addition, we show that EGFRis induce autophagy in colorectal cancer cells, which is important for cell survival in the setting of combined treatment with an EGFRi and menin inhibitor. Inhibition of autophagy with chloroquine further sensitizes colorectal cancers to treatment with the combination of an EGFRi and menin inhibitor. Together, these findings uncover a novel role for menin in colorectal cancer as a repressor of glycolysis and demonstrate that menin inhibitor-induced increases in glycolysis sensitize colorectal cancer cells to EGFRis. In addition, these findings illustrate the importance of autophagy as a protective mechanism against EGFRis, especially in the presence of menin inhibition. Ultimately, these data open the possibility of using menin-mediated regulation of glycolysis to potentially improve treatment modalities for colorectal cancer.