Article
Chemistry, Multidisciplinary
Jia-hui Tian, Qian Wu, Yong-xiang He, Qi-ying Shen, Mubarak Rekep, Gui-ping Zhang, Jian-dong Luo, Qin Xue, Ying-hua Liu
Summary: Zonisamide (ZNS) attenuates ER stress-induced apoptosis, improves cardiac dysfunction and hypertrophy in diabetic mice, suggesting its protective effects on diabetic cardiomyopathy.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Food Science & Technology
Haidy E. Michel, Mariam M. Tadros, Moataz S. Hendy, Shereen Mowaka, Bassam M. Ayoub
Summary: This study demonstrates the potential neuroprotective effect of omarigliptin (OG) in a rat model of Parkinson's disease. OG attenuated motor impairment, histological aberrations, alpha-synuclein accumulation, and rescued dopaminergic neurons. It also halted oxidative stress, neuroinflammation, apoptosis, and endoplasmic reticulum stress. These findings suggest that OG could be repurposed as a novel neuroprotective agent.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Neurosciences
Katarzyna Mnich, Shirin Moghaddam, Patrick Browne, Timothy Counihan, Stephen P. Fitzgerald, Kenneth Martin, Ciaran Richardson, Afshin Samali, Adrienne M. Gorman
Summary: ER stress-regulated proteins in blood may serve as diagnostic biomarkers for Parkinson's disease (PD).
MOLECULAR NEUROBIOLOGY
(2023)
Article
Immunology
Zongran Liu, Yang Huang, Xuejing Wang, Jia-Yi Li, Can Zhang, Ying Yang, Jing Zhang
Summary: Peripheral inflammation in Parkinson's disease is closely related to central nervous system pathology. The discovery of meningeal lymphatics and its involvement in PD provides important insights into the underlying mechanisms of peripheral inflammation. This study using an A53T mouse model found structural and functional alterations in the deep cervical lymph node, which contribute to peripheral inflammation in PD. In addition, inhibiting endoplasmic reticulum stress shows potential for therapeutic intervention in PD pathogenesis.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Chemistry, Multidisciplinary
Longping Yao, Fengfei Lu, Sumeyye Koc, Zijian Zheng, Baoyan Wang, Shizhong Zhang, Thomas Skutella, Guohui Lu
Summary: The gene mutations of LRRK2 are associated with Parkinson's disease. The G2019S mutation promotes endoplasmic reticulum stress and neural death by interacting with THBS1/TGF-beta 1. These findings provide important insights into the pathogenesis of Parkinson's disease and potential therapeutic targets.
Article
Biochemistry & Molecular Biology
Hugo J. R. Fernandes, Josh P. P. Kent, Michaela Bruntraeger, Andrew R. R. Bassett, Albert Koulman, Emmanouil Metzakopian, Stuart G. G. Snowden
Summary: The metabolic basis of Parkinson's disease is poorly understood, but it is known that mitochondrial and endoplasmic reticulum stress play a role in the pathology. In this study, the effects of mitochondrial and ER stress on dopamine neuron metabolism were examined, and it was found that both stresses caused significant dysregulation of metabolism, with triglyceride accumulation being a major driver. Understanding the mechanisms of triglyceride accumulation could lead to new therapeutic approaches.
Article
Chemistry, Multidisciplinary
Qian Wu, Jia-hui Tian, Yong-xiang He, Yong-yin Huang, Yu-qing Huang, Gui-ping Zhang, Jian-dong Luo, Qin Xue, Xi-yong Yu, Ying-hua Liu
Summary: Zonisamide has been shown to alleviate cardiac hypertrophy by increasing Hrd1 expression and inhibiting ER stress in rats. This drug significantly improves cardiac function, reduces cardiac hypertrophy and fibrosis, suppresses apoptosis and ER stress in experimental models of pathological cardiac hypertrophy.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Cell Biology
Sonam Gupta, Amit Mishra, Sarika Singh
Summary: The study demonstrated that salubrinal provided significant protection against rotenone-induced adverse effects on dopaminergic neurons, suggesting its potential therapeutic utility in Parkinson's disease by attenuating progressive neuronal death and pathological alterations.
CELLULAR SIGNALLING
(2021)
Article
Biochemistry & Molecular Biology
Mahmoud A. Desouky, Mina Y. George, Haidy E. Michel, Doaa A. Elsherbiny
Summary: This study found that roflumilast, a phosphodiesterase-4 inhibitor, has a neuroprotective effect in a rat model of Parkinson's disease. It reduces motor impairment, brain lesions, and loss of dopaminergic neurons, and decreases the accumulation of misfolded α-synuclein. Roflumilast enhances proteasome activity, inhibits endoplasmic reticulum stress and oxidative stress, and shows significant anti-apoptotic activity. This study suggests that roflumilast can be repurposed as a novel neuroprotective drug to restore protein homeostasis.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Analytical
Ming Yan, Haixiao Fang, Xiaoqing Wang, Jiajia Xu, Chengwu Zhang, Li Xu, Lin Li
Summary: Endoplasmic reticulum (ER) stress is involved in diseases like Parkinson's disease, with peroxynitrite being a pivotal factor. A two-photon fluorescence probe, ER-PN, was designed and synthesized for visualizing ER peroxynitrite in PD models. The probe showed rapid and highly selective response to peroxynitrite in vitro, making it a promising tool for imaging peroxynitrite in ER stress-related diseases.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Review
Immunology
Jana Messias Sandes, Regina Celia Bressan Queiroz de Figueiredo
Summary: The endoplasmic reticulum (ER) is an important organelle in higher eukaryotic cells responsible for protein folding and assembly. It undergoes strict quality control to ensure proper processing of proteins, with unfolded proteins being targeted for degradation through the ER-associated degradation (ERAD) complex. Additionally, the ER responds to stress through the unfolded protein response (UPR) to restore homeostasis or induce cell death. Protozoan parasites such as Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp. also have similar ER structures and stress response mechanisms, making them attractive targets for chemotherapy.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Cell Biology
Ruiyuan Xu, Jianlu Song, Rexiati Ruze, Yuan Chen, Xinpeng Yin, Chengcheng Wang, Yupei Zhao
Summary: This study reveals squalene epoxidase (SQLE) as a novel oncogene that promotes pancreatic cancer (PC) growth by mitigating endoplasmic reticulum stress and activating lipid raft-regulated Src/PI3K/Akt signaling pathway. SQLE facilitates cell proliferation, induces cell cycle progression, and inhibits apoptosis in vitro, while promoting tumor growth in vivo. SQLE inhibitors effectively suppress PC cell proliferation and xenograft tumor growth, highlighting the potential of SQLE as a therapeutic target for PC.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Gunes Parlakgul, Ana Paula Arruda, Song Pang, Erika Cagampan, Nina Min, Ekin Guney, Grace Yankun Lee, Karen Inouye, Harald F. Hess, C. Shan Xu, Gokhan S. Hotamisligil
Summary: This study reveals the complex structural organization of organelles in liver tissue and highlights the significant alterations in obese mice. The functional importance of these structural changes on cellular and systemic metabolism is also demonstrated.
Article
Biochemistry & Molecular Biology
Jun Chen, Zhiwei Zheng, Mingqi Li, Chengkun Cao, Xuli Zhou, Bozhen Wang, Xin Gan, Zhicheng Huang, Yugang Liu, Wenting Huang, Fei Liang, Keyang Chen, Yeli Zhao, Xue Wang, Jianzhang Wu, Li Lin
Summary: A stable and less cytotoxic monoketene compound (S2) has been discovered as a potential therapeutic agent for Parkinson's disease (PD). In vitro and in vivo experiments showed significant neuroprotective effects of this compound, which is achieved by activating the AKT pathway and suppressing endoplasmic reticulum stress. These findings provide evidence for the clinical significance of this compound in protecting dopaminergic neurons in PD.
BIOORGANIC CHEMISTRY
(2023)
Review
Clinical Neurology
Shubhangini Tiwari, Sarika Singh
Summary: Parkinson's disease is characterized by dopaminergic neuronal degeneration and death, with complex pathological mechanisms. Understanding the role of nitric oxide, endoplasmic reticulum stress, and the ubiquitin proteasome system in PD pathology, particularly the regulatory functions of ubiquitin ligases, is crucial for grasping disease etiology and identifying potential therapeutic targets.
Article
Clinical Neurology
Tetsuya Yamada, Shohei Tsuji, Shinsuke Nakamura, Yusuke Egashira, Masamitsu Shimazawa, Noriyuki Nakayama, Hirohito Yano, Toru Iwama, Hideaki Hara
Summary: Riluzole demonstrates significant growth-inhibitory effects on all GBM cell lines in a time- and dose-dependent manner. It synergistically enhances the antitumor effect of TMZ in MGMT-positive GBM cell lines, while suppressing MGMT expression and TMZ-induced MGMT upregulation. Combinatorial TMZ/riluzole treatment significantly suppresses tumor growth in an intracranial MGMT-positive GBM model, suggesting it as a promising therapeutic regimen for MGMT-positive GBMs.
JOURNAL OF NEUROSURGERY
(2021)
Article
Ophthalmology
Kyoko Ishida, Yukimichi Nakano, Kazuki Ojino, Masamitsu Shimazawa, Tomohiro Otsuka, Satoshi Inagaki, Kazuhide Kawase, Hideaki Hara, Tetsuya Yamamoto
Summary: The characteristics of conjunctival bleb play a crucial role in the success of glaucoma filtering surgery. Research comparing bleb histology after three different glaucoma surgeries found that trabeculectomy and EX-PRESS groups had significantly lower postoperative IOP at 2 weeks than the silicone tube group, but no significant differences thereafter. Bleb survival and vascularity were similar among the groups, but bleb thickness was greater in all experimental groups compared to controls. Inflammation postoperatively was correlated with the thickness of the bleb wall.
OPHTHALMIC RESEARCH
(2021)
Article
Clinical Neurology
Satoshi Inagaki, Masamitsu Shimazawa, Wataru Otsu, Tomoaki Araki, Yosuke Numata, Shinsuke Nakamura, Hideshi Tsusaki, Hideaki Hara
Summary: The study created an RVO model in non-human primates and investigated the effects of ranibizumab on retinal pathology related to RVO.
CURRENT NEUROVASCULAR RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Kodai Ishida, Tomohiro Yako, Miruto Tanaka, Wataru Otsu, Shinsuke Nakamura, Masamitsu Shimazawa, Hideshi Tsusaki, Hideaki Hara
Summary: The corneal epithelium is susceptible to damage from UV and blue LED light exposure, leading to eye diseases. NSP-116 has been shown to protect corneal cells from oxidative stress induced by these lights, reducing cell death and preserving mitochondrial function, ultimately preventing eye diseases.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2021)
Article
Neurosciences
Shohei Tsuji, Shinsuke Nakamura, Tetsuya Yamada, Susana de Vega, Yasunori Okada, Shintaro Inoue, Masamitsu Shimazawa, Hideaki Hara
Summary: The study highlights the significant role of hyaluronan binding protein in glioblastoma, with its deficiency inhibiting cell proliferation and migration, and increasing cell death. Mouse experiments also confirmed these findings, suggesting potential therapeutic targets in the tumor microenvironment of glioblastoma.
Article
Clinical Neurology
Miruto Tanaka, Yuki Inoue, Takahiko Imai, Norifumi Tanida, Koichi Takahashi, Hideaki Hara
Summary: This study demonstrated that alpha 2-adrenergic agonists guanabenz and clonidine inhibit VEGF-induced retinal endothelial cell growth and migration, and reduce CNV lesion sizes in a CNV model. Continuous administration of guanabenz also attenuated CNV size and leakage from neovessels, suggesting potential as a novel therapeutic drug for patients with neovascular AMD.
CURRENT NEUROVASCULAR RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Hiroto Yasuda, Miruto Tanaka, Anri Nishinaka, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara
Summary: Neovascular age-related macular degeneration (nAMD) with choroidal neovascularization (CNV) is a major cause of irreversible blindness in the elderly. The integrated stress response (ISR) plays a key role in nAMD, with ATF4 potentially promoting angiogenesis in endothelial cells. Treatment with ISR inhibitor ISRIB can decrease CNV formation, vascular leakage, and VEGF levels, suggesting a potential therapeutic target for nAMD patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Kei Takahashi, Shinsuke Nakamura, Wataru Otsu, Masamitsu Shimazawa, Hideaki Hara
Summary: The study indicates that PGRN deficiency activates lysosomal function in Iba-1(+) cells, leading to abnormal inflammation. This aberrant activation may contribute to the progression of CNV, and regulating these cells could be a novel therapeutic target for exudative AMD.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Ophthalmology
Wataru Morozumi, Kota Aoshima, Satoshi Inagaki, Yuki Iwata, Yuya Takagi, Shinsuke Nakamura, Hideaki Hara, Masamitsu Shimazawa
Summary: Glaucoma is a neurodegenerative disease that causes blindness, and reducing intraocular pressure (IOP) is crucial for its treatment. This study reveals that activating Piezo1 can lower IOP and suppress the accumulation of fibronectin. Activation of Piezo1 leads to increased expression of matrix metalloproteinase-2 (MMP-2) and cyclooxygenase (COX)-2, while decreasing the expression of fibronectin. Furthermore, Piezo1 activation promotes the arachidonic acid cascade, increasing the secretion of prostaglandin F2 alpha (PGF2 alpha) and the expression of MMP-2.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Tomohiro Yako, Wataru Otsu, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara
Summary: This study investigated the effect of lipid droplet accumulation on RPE function, and found that inhibiting lipid droplet formation may be a target for preventing and treating non-exudative AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Correction
Pharmacology & Pharmacy
Hirofumi Matsubara, Takahiko Imai, Shohei Tsuji, Natsumi Oka, Yusuke Egashira, Yukiko Enomoto, Noriyuki Nakayama, Shinsuke Nakamura, Masamitsu Shimazawa, Toru Iwama, Hideaki Hara
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Honoka Fujimori, Takuya Ohba, Masashi Mikami, Shinsuke Nakamura, Kenichi Ito, Hiroyuki Kojima, Tatsuji Takahashi, Arunasiri Iddamalgoda, Masamitsu Shimazawa, Hideaki Hara
Summary: Alzheimer's disease is characterized by progressive cognitive decline, with increasing global incidences. Oxidative stress and endoplasmic reticulum stress are implicated in neuronal cell death and cognitive dysfunction. Centella asiatica and its active component araliadiol demonstrate neuroprotective effects, potentially preventing cognitive impairment in AD.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Hirofumi Matsubara, Takahiko Imai, Shohei Tsuji, Natsumi Oka, Yusuke Egashira, Yukiko Enomoto, Noriyuki Nakayama, Shinsuke Nakamura, Masamitsu Shimazawa, Toru Iwama, Hideaki Hara
Summary: The study found that nafamostat did not significantly affect cerebral blood flow or SAH grade but improved neurological behavior and suppressed the expression of thrombin and MMP-9. In vitro studies showed that nafamostat had a protective effect on HBMVECs exposed to thrombin and hypoxia, suggesting its potential for improving neurological outcomes after SAH.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Wataru Otsu, Kodai Ishida, Naoki Chinen, Shinsuke Nakamura, Masamitsu Shimazawa, Hideshi Tsusaki, Hideaki Hara
Summary: This study investigated the cellular injury caused by cigarette smoke extract (CSE) or heated tobacco products (HTPs) on corneal epithelial cells. The results showed that exposure to CSE disrupted tight junctions, increased cell volume, decreased transepithelial electrical resistance, and induced lipid peroxidation as well as ferrous ion accumulation. Additionally, exposure to either CSE or HTPs activated the ferroptosis signaling pathway, leading to corneal epithelial cell injury.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Takamasa Kinoshita, Hiroyuki Tomita, Hideshi Okada, Ayumi Niwa, Fuminori Hyodo, Tomohiro Kanayama, Mikiko Matsuo, Yuko Imaizumi, Takahiro Kuroda, Yuichiro Hatano, Masafumi Miyai, Yusuke Egashira, Yukiko Enomoto, Noriyuki Nakayama, Shigeyuki Sugie, Kazu Matsumoto, Yu Yamaguchi, Masayuki Matsuo, Hideaki Hara, Toru Iwama, Akira Hara
Summary: Reduced expression of Heparan sulfate in the vascular endothelium of the brain can suppress glioblastoma growth and neovascularization in mice.