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Molecules, Vol. 27, Pages 3151: Neuroprotective Effect of Dioscin against Parkinson & rsquo;s Disease via Adjusting Dual-Specificity phosphatase 6(DUSP6)-Mediated Oxidative Stress
In this study, the tests on 6-hydroxydopamine (6-OHDA)-induced PC12 cells and rats were carried out. The results showed that dioscin dramatically improved cell viability, decreased reactive oxygen species (ROS) levels, improved motor behavior and tyrosine hydroxylase(TH) levels and restored the levels of glutathione (GSH) and malondialdehyde (MDA) in rats. Mechanism investigation showed that dioscin not only markedly increased the expression level of dual- specificity phosphatase 6 (DUSP6) by 1.87-fold in cells and 2.56-fold in rats, and decreased phospho-extracellular regulated protein kinases (p-ERK) level by 2.12-fold i...
Source: Molecules - May 14, 2022 Category: Chemistry Authors: Zhang Mao Meng Gao Xuerong Zhao Lili Li Jinyong Peng Tags: Article Source Type: research

Chronic treatment with the complex I inhibitor MPP+ depletes endogenous PTEN-induced kinase 1 (PINK1) via up-regulation of Bcl-2-associated athanogene 6 (BAG6) Neurobiology
Mitochondrial dysfunction is implicated in sporadic and familial Parkinson's disease (PD). However, the mechanisms that impair homeostatic responses to mitochondrial dysfunction remain unclear. Previously, we found that chronic, low-dose administration of the mitochondrial complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+) dysregulates mitochondrial fission–fusion, mitophagy, and mitochondrial biogenesis. Given that PTEN-induced kinase 1 (PINK1) regulates mitochondrial function, dynamics, and turnover, we hypothesized that alterations in endogenous PINK1 levels contribute to depletion of mitochondria during chronic c...
Source: Journal of Biological Chemistry - June 4, 2020 Category: Chemistry Authors: Manish Verma, Jianhui Zhu, Kent Z. Q. Wang, Charleen T. Chu Tags: Molecular Bases of Disease Source Type: research

A dual druggable genome-wide siRNA and compound library screening approach identifies modulators of parkin recruitment to mitochondria Molecular Bases of Disease
Genetic and biochemical evidence points to an association between mitochondrial dysfunction and Parkinson's disease (PD). PD-associated mutations in several genes have been identified and include those encoding PTEN-induced putative kinase 1 (PINK1) and parkin. To identify genes, pathways, and pharmacological targets that modulate the clearance of damaged or old mitochondria (mitophagy), here we developed a high-content imaging-based assay of parkin recruitment to mitochondria and screened both a druggable genome-wide siRNA library and a small neuroactive compound library. We used a multiparameter principal component analy...
Source: Journal of Biological Chemistry - March 5, 2020 Category: Chemistry Authors: Helen L. Scott, Nicola Buckner, Francesc Fernandez-Albert, Elisa Pedone, Lorena Postiglione, Gongyu Shi, Nicholas Allen, Liang-Fong Wong, Lorenzo Magini, Lucia Marucci, Gregory A. O'Sullivan, Sarah Cole, Justin Powell, Peter Maycox, James B. Uney Tags: Neurobiology Source Type: research

The ubiquitin E3 ligase CHIP promotes proteasomal degradation of the serine/threonine protein kinase PINK1 during staurosporine-induced cell death Cell Biology
In this study, we demonstrate that the ubiquitin E3 ligase carboxyl terminus of Hsp70-interacting protein (CHIP) promotes PINK1 ubiquitination and decreases its steady-state levels. Moreover, PINK1 levels were strongly reduced in HEK293 and SH-SY5Y cells exposed to the apoptosis-inducer staurosporine. Of note, we found that this reduction resulted from CHIP-mediated PINK1 ubiquitination. Accordingly, siRNA-mediated CHIP knockdown reduced susceptibility to staurosporine-induced cell death. Taken together, these findings suggest that CHIP plays a role in negative regulation of PINK1 stability and may suppress PINK1's cytopro...
Source: Journal of Biological Chemistry - January 26, 2018 Category: Chemistry Authors: Lang Yoo, Kwang Chul Chung Tags: Protein Synthesis and Degradation Source Type: research

Up-regulation of Pin1 in Parkinson Disease Neurobiology
Parkinson disease (PD) is a chronic neurodegenerative disease characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra. The pathophysiological mechanisms underlying PD remain unclear. Pin1, a major peptidyl-prolyl isomerase, has recently been associated with certain diseases. Notably, Ryo et al. (Ryo, A., Togo, T., Nakai, T., Hirai, A., Nishi, M., Yamaguchi, A., Suzuki, K., Hirayasu, Y., Kobayashi, H., Perrem, K., Liou, Y. C., and Aoki, I. (2006) J. Biol. Chem. 281, 4117–4125) implicated Pin1 in PD pathology. Therefore, we sought to systematically characterize the role of Pin1 in P...
Source: Journal of Biological Chemistry - July 26, 2013 Category: Chemistry Authors: Ghosh, A., Saminathan, H., Kanthasamy, A., Anantharam, V., Jin, H., Sondarva, G., Harischandra, D. S., Qian, Z., Rana, A., Kanthasamy, A. G. Tags: Molecular Bases of Disease Source Type: research