Review
Toxicology
Chang Liu, Rong Ju
Summary: Manganese (Mn) is a trace element involved in various physiological processes, but overexposure to Mn is associated with neurodegenerative disorders and neuronal apoptosis. The mechanisms of Mn-induced neuronal apoptosis include reactive oxygen species generation, neuroinflammation, protein accumulation, endoplasmic reticulum stress (ER stress), and autophagy. ER stress and autophagy both have dual roles in cell protection and injury, and their relationship in Mn-induced neurotoxicity is still unclear. This review discusses the mechanisms and connections between ER stress, autophagy, and apoptosis, providing a new perspective on Mn-induced neuronal apoptosis and neurodegenerative diseases.
TOXICOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Daniela D. Queiroz, Thales de P. Ribeiro, Julliana M. Goncalves, Larissa M. M. Mattos, Ellen Gerhardt, Julia Freitas, Fernando L. Palhano, Susana Frases, Anderson S. Pinheiro, Malachy McCann, Andrew Knox, Michael Devereux, Tiago F. Outeiro, Marcos D. Pereira
Summary: The overproduction of reactive oxygen species (ROS) induces oxidative stress, which is associated with aging and various human pathologies. This study investigates the antioxidant activity of a water-soluble Mn2+-complex and its ability to attenuate alpha-synuclein toxicity and aggregation. The Mn2+-complex exhibits significant antioxidant potential and increases the activity of intracellular antioxidant enzymes, while also reducing alpha-synuclein oligomerization and aggregation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Environmental Sciences
Yiqi Wang, Lian Duan, Xing Zhang, Yang Jiao, Ying Liu, Lingling Dai, Hong Yan
Summary: The study demonstrated that chronic exposure to ACR can impair motor skills, muscle strength, and coordination in rats, as well as damage the morphology of the cerebellum, leading to increased apoptosis and initiation of autophagy.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Review
Chemistry, Multidisciplinary
Yasaman Esmaeili, Zahra Yarjanli, Fatemeh Pakniya, Elham Bidram, Marek J. Los, Mehdi Eshraghi, Daniel J. Klionsky, Saeid Ghavami, Ali Zarrabi
Summary: Protein homeostasis is crucial for cell function, and disruption of the molecular mechanisms involved in this process may contribute to neurodegenerative diseases. Autophagy disruption, oxidative stress, and ER stress are the main molecular mechanisms underlying neurodegeneration, and they have synergistic effects on each other. Therefore, targeting the crosstalk between these pathways may play a critical role in healing neurodegenerative diseases.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Xiaoqing Mi, Qijun Li, Xiaoming Wen, Junxia Xie, Youcui Wang, Ning Song
Summary: The research indicates that extracellular alpha-synuclein can regulate cellular iron metabolism, potentially mediated by ER stress. This provides novel evidence to elucidate the relationships between transmitted alpha-synuclein and iron metabolism disturbance in PD.
NEUROCHEMICAL RESEARCH
(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
Biology
Irene Riera-Tur, Tillman Schaefer, Daniel Hornburg, Archana Mishra, Miguel da Silva Padilha, Lorena Fernandez-Mosquera, Dennis Feigenbutz, Patrick Auer, Matthias Mann, Wolfgang Baumeister, Rudiger Klein, Felix Meissner, Nuno Raimundo, Ruben Fernandez-Busnadiego, Irina Dudanova
Summary: This study investigates the effects of protein aggregates on primary neurons. It was found that the aggregates impair the late stages of autophagy, resulting in lysosomal alterations and neurotoxicity. The study also identifies the interaction between β proteins and the AP-3 adaptor complex, which leads to lysosomal defects.
LIFE SCIENCE ALLIANCE
(2022)
Article
Cell Biology
Cailing Wen, Yuheng Zhou, Yanting Xu, Huijing Tan, Caixia Pang, Haiqian Liu, Kaifei Liu, Linlin Wei, Hui Luo, Tian Qin, Chonghua He, Cuiling Liu, Chun Zhou
Summary: The lack of GBF1 affects osteoclast differentiation, leading to cell swelling and reduced formation; GBF1 inhibition can intensify cellular stress and excessive autophagy, ultimately leading to cell apoptosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yue Gu, Huan Xia, Xiao Chen, Jing Li
Summary: This study demonstrated that CUR-loaded nanoparticles can protect cardiomyocytes from lipotoxic injury induced by palmitate, reverse the decrease in cell proliferation, inhibit apoptosis, and activate the autophagy pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
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
Multidisciplinary Sciences
Dongmei Liu, Muriel Mari, Xia Li, Fulvio Reggiori, Susan Ferro-Novick, Peter Novick
Summary: This study discovered a process called ER-phagy, which selectively delivers fragments of the endoplasmic reticulum to the lysosome or vacuole in response to starvation or the accumulation of misfolded proteins. The loss of specific genes and proteins blocks the association between the autophagy receptor and the assembly scaffold protein, and a membrane contact site module is also found to be involved in ER-phagy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Environmental Sciences
Zaiwei Wu, Fang Wang, Liwen Hu, Jianrong Zhang, Daojun Chen, Sujuan Zhao
Summary: This study demonstrates that MCLR causes damage to the male reproductive system and enhances autophagy, indicating the essential role of autophagy in MCLR-induced cell death. Furthermore, the study reveals the involvement of ER stress-related autophagy pathway in MCLR-induced apoptosis and injury in the male reproductive system.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Environmental Sciences
Yu Wang, Hongjing Zhao, Mengyao Mu, Menghao Guo, Mingwei Xing
Summary: Arsenic accumulation in the spleen due to environmental exposure can cause severe injuries, while zinc treatment may offer protection against arsenic-induced splenic toxicity in common carp.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Environmental Sciences
Rulin Ma, Bei Li, Cheng Zhang, Rongrong Lei, Xiao Zhang, Chao Wang, Shun Zhang, Aiguo Wang
Summary: Research indicates that PBDE-47 damages thyroid tissues by triggering endoplasmic reticulum stress, apoptosis, and autophagy, and these changes can be reversed by 4-Phenylbutyric acid.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Environmental Sciences
Zhaoqi He, Peng Shen, Lianjun Feng, Haoyang Hao, Yuhong He, Guyue Fan, Zhuoyu Liu, Kun Zhu, Yiqi Wang, Naisheng Zhang, Xiaoyu Hu, Yunhe Fu, Jiacheng Wu
Summary: Cadmium-induced liver toxicity is associated with ferroptosis, which is involved in oxidative stress, autophagy, and endoplasmic reticulum stress.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)