Article
Cell Biology
Haizhe Ji, Jin Wang, David Muid, Wei Song, Yinong Jiang, Hao Zhou
Summary: The mitochondrial unfolded protein response (UPRmt) is an adaptive transcriptional response that degrades abnormal or unfolded proteins through activation of proteases, chaperones, and antioxidant enzymes to restore mitochondrial function. It plays a cardioprotective role in myocardial ischemia/reperfusion (I/R) injuries by regulating oxidative stress, apoptosis-related proteins, and mitochondrial quality control mechanisms.
CELLULAR SIGNALLING
(2022)
Article
Biochemistry & Molecular Biology
Maria Paschou, Panagiota Papazafiri, Chrysanthi Charalampous, Michael Zachariadis, Skarlatos G. Dedos, Epaminondas Doxakis
Summary: This study reveals that miR-124-3p and miR-153-3p regulate the expression of RyRs and IP(3)Rs, and maintain Ca2+ homeostasis by reducing ER Ca2+ release. Furthermore, these miRNAs alleviate cytosolic Ca2+ overload and protect protein-folding capacity by attenuating PERK signaling.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Li-Tzu Chen, Chih-Ta Lin, Liang-Yi Lin, Jiun-Min Hsu, Yu-Chun Wu, Chun-Liang Pan
Summary: In C. elegans, loss of neuronal fzo-1/mito-fusin induces nonautonomous UPRmt through multiple neurotransmitters and neurohormones. This triggers nonautonomous mitochondrial fragmentation, requiring genes involved in autophagy and mitophagy. The systemic activation of UPRmt and mitochondrial fragmentation improves resistance to pathogenic Pseudomonas infection in C. elegans.
DEVELOPMENTAL CELL
(2021)
Review
Cell Biology
Giuseppe Chiantia, Enis Hidisoglu, Andrea Marcantoni
Summary: Research into the early impacts of Alzheimer's disease on synapse function is a promising approach to finding a treatment. Recent studies have shown that the accumulation of Abeta42 peptide, which arises from the processing of APP, targets RyRs in hippocampal neurons, leading to the release of calcium from the ER and subsequent dysregulation of calcium concentration. This dysregulation is a hallmark of Alzheimer's disease and other neurodegenerative diseases. This review aims to summarize the current understanding of the role of RyRs in neuronal function under physiological conditions and during the onset of Alzheimer's disease.
Article
Neurosciences
Marijn Kuijpers, Gaga Kochlamazashvili, Alexander Stumpf, Dmytro Puchkov, Aarti Swaminathan, Max Thomas Lucht, Eberhard Krause, Tanja Maritzen, Dietmar Schmitz, Volker Haucke
Summary: This study demonstrates that loss of neuronal autophagy leads to selective accumulation of tubular endoplasmic reticulum (ER) in axons, resulting in increased excitatory neurotransmission and compromised postnatal viability in vivo. The elevated excitatory neurotransmission is caused by increased calcium release from ER stores via ryanodine receptors accumulated in axons and at presynaptic sites. Neuronal autophagy controls axonal ER calcium stores to regulate neurotransmission in healthy neurons and in the brain.
Article
Clinical Neurology
Noemi Esteras, Olga Kopach, Marta Maiolino, Vincenzo Lariccia, Salvatore Amoroso, Seema Qamar, Selina Wray, Dmitri A. Rusakov, Morana Jaganjac, Andrey Y. Abramov
Summary: The study found that overproduction of mitochondrial reactive oxygen species (ROS) in 10+16 neurons alters the trafficking of specific glutamate receptor subunits, leading to impaired glutamatergic signaling, calcium overload, and excitotoxicity. Mitochondrial antioxidants can restore the altered response and prevent neuronal death. Additionally, extracellular 4R tau induces the same pathological response in healthy neurons, proposing a mechanism for disease propagation.
ALZHEIMERS & DEMENTIA
(2022)
Article
Neurosciences
Yulim Lee, Jun Young Heo, Xianshu Ju, Jianchen Cui, Min Jeong Ryu, Min Joung Lee, Boohwi Hong, Sungho Yoo, Jeonghoon Ahn, Yoon Hee Kim, Youngkwon Ko, Woosuk Chung
Summary: The study shows that general anesthesia induces changes in dendritic spine number and synaptic transmission in developing mice, potentially related to neurodevelopmental disorders. Additionally, mitochondrial function and UPRmt may serve as potential targets for preventing anesthesia toxicity.
Article
Biochemistry & Molecular Biology
E. D'Acunto, L. Gianfrancesco, I Serangeli, M. D'Orsi, V Sabato, N. A. Guadagno, G. Bhosale, S. Caristi, A. Failla, A. De Jaco, E. Cacci, M. R. Duchen, G. Lupo, G. Galliciotti, E. Miranda
Summary: In this study, the mechanism of neurodegeneration in FENIB was investigated using a transgenic neural progenitor cell model. The research found that polymerogenic NS caused mitochondrial alterations and affected the interaction between the endoplasmic reticulum and mitochondria.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Feng Li, Dengxing Lun, Dayong Liu, Zesen Jia, Zhenye Zhu, Zhiqiang Liu, Xiaopeng Li
Summary: Bone marrow stromal cells (BMSCs) undergo senescence with aging, leading to increased adipogenesis and decreased osteoblastogenesis, contributing to senile osteoporosis. The protein disulfide isomerase PDI-6 plays an important role in mitochondrial unfolded protein response and maintenance of mitochondrial homeostasis. Melatonin enhances PDI-6 expression and repairs injured mitochondria, and PDI-6 is a downstream effector of Wnt/b-catenin pathway. This study suggests that PDI-6 is a pharmacological target for melatonin intervention in age-related osteoporosis by mitigating mitochondrial dysfunction in senescent BMSCs.
Article
Biochemistry & Molecular Biology
Xiaolei Lian, Xiaoyi Wang, Yinyin Xie, Hanqing Sheng, Jiao He, Tingting Peng, Nanchang Xie, Cui Wang, Yajun Lian
Summary: ATF5-regulated mitochondrial unfolded protein response (mtUPR) exerts neuroprotective effects against seizures-induced neuronal injury and apoptosis, potentially mediated by the modulation of mitochondrial reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress.
NEUROCHEMICAL RESEARCH
(2023)
Article
Cell Biology
Sager Nawafleh, Abdallah Barjas Qaswal, Aiman Suleiman, Obada Alali, Fuad Mohammed Zayed, Mohammad Abu Orabi Al-Adwan, Mo'ath Bani Ali
Summary: GABA receptors mediate inhibitory effects in the nervous system by hyperpolarizing the resting membrane potential through the influx of chloride ions. However, under certain conditions such as early neuronal development or mutations, chloride ions can depolarize the resting membrane potential through quantum tunneling.
Article
Biochemistry & Molecular Biology
Lin Lin Song, Yuan Qing Qu, Yong Pei Tang, Xi Chen, Hang Hong Lo, Li Qun Qu, Yun Xiao Yun, Vincent Kam Wai Wong, Rui Long Zhang, Hui Miao Wang, Meng Han Liu, Wei Zhang, Hui Xia Zhang, Joyce Tsz Wai Chan, Cai Ren Wang, Jian Hui Wu, Betty Yuen Kwan Law
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by cognitive decline. The beta-amyloid pathway plays a vital role in neuronal apoptosis through altering Ca2+ signaling. In this study, a flavonol glycoside, hyperoside, was identified with anti-A beta aggregation, BACE inhibition, and neuroprotective effects. Pharmacokinetic analysis showed higher brain bioavailability of hyperoside via intranasal administration, and further in vivo studies demonstrated its ability to improve motor deficits, spatial memory, learning ability, and reduce A beta plaques in Alzheimer's disease mice model. Hyperoside was found to interact with A beta and ryanodine receptors, regulating cellular apoptosis via the endoplasmic reticulum-mitochondrial calcium signaling pathway. Moreover, it increased Bcl2, decreased Bax and cyto-c levels, and ameliorated neuronal cell death. These findings suggest that hyperoside could be a potential therapeutic agent or preventive remedy for Alzheimer's disease.
Article
Neurosciences
Qianyun Yu, Ruijie Zhang, Tianjing Li, Liu Yang, Zhihan Zhou, Long Hou, Wen Wu, Rui Zhao, Xiaoling Chen, Yajie Yao, Shile Huang, Long Chen
Summary: Defective autophagy is involved in the development of Parkinson's disease (PD), and PD toxins impede autophagy through the PTEN/Akt signaling pathway, leading to neuronal apoptosis. Activation of PTEN and inactivation of Akt by PD toxins inhibit autophagy, and this process is regulated by the protein Parkin. Manipulation of PTEN/Akt/autophagy signaling with antioxidants could be a potential therapeutic strategy for preventing neuronal loss in PD.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Immunology
Hongming Sun, Xitong Li, Xin Chen, Yingquan Xiong, Yaochen Cao, Ziqiang Wang
Summary: This study demonstrates that Drp1 plays a promotive role in mitochondrial fragmentation, leading to neuronal injury in CKD induced by hypercalcemia. The mechanism may involve the increase of mitochondrial fragmentation and ROS generation.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Engineering, Environmental
Jing Zheng, Shane Antrobus, Wei Feng, Trevor N. Purdy, Bradley S. Moore, Isaac N. Pessah
Summary: This study found that bromopyrroles can influence neuronal network activity, with higher concentrations of TBP leading to a slow and sustained elevation in cytoplasmic calcium levels, ultimately resulting in loss of neuronal viability. The potential ecological and health impacts of bromopyrroles warrant further investigation.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Peng Zheng, Benhua Zeng, Meiling Liu, Jianjun Chen, Junxi Pan, Yu Han, Yiyun Liu, Ke Cheng, Chanjuan Zhou, Haiyang Wang, Xinyu Zhou, Siwen Gui, Seth W. Perry, Ma-Li Wong, Julio Licinio, Hong Wei, Peng Xie
Article
Chemistry, Multidisciplinary
Peng Zheng, Jian Yang, Yifan Li, Jing Wu, Weiwei Liang, Bangmin Yin, Xunmin Tan, Yu Huang, Tingjia Chai, Hanping Zhang, Jiajia Duan, Jingjing Zhou, Zuoli Sun, Xu Chen, Subhi Marwari, Jianbo Lai, Tingting Huang, Yanli Du, Peifen Zhang, Seth W. Perry, Ma-Li Wong, Julio Licinio, Shaohua Hu, Peng Xie, Gang Wang
Letter
Psychiatry
Stephen Bacchi, Adon Asahina, David Wang, Morganne Wagner, Monique Pisaniello, Jamie French, Yiran Tan, Seth W. Perry, Ian Symonds, Megan Anakin, Tim Wilkinson, Stephen J. Gallagher, Ma-Li Wong, Patrick McGorry, Julio Licinio
AUSTRALASIAN PSYCHIATRY
(2020)
Article
Biochemistry & Molecular Biology
Peng Zheng, Jing Wu, Hanping Zhang, Seth W. Perry, Bangmin Yin, Xunmin Tan, Tingjia Chai, Weiwei Liang, Yu Huang, Yifan Li, Jiajia Duan, Ma-Li Wong, Julio Licinio, Peng Xie
Summary: Recent research has shown that changes in the microbiota-gut-brain (MGB) axis are associated with the onset of depression, with disruptions in microbial composition and metabolic signatures in nonhuman primates displaying depressive-like behaviors. The study identified specific disturbances in the Firmicutes phylum and alterations in microbiota and metabolic clusters related to fatty acyl, sphingolipid, and glycerophospholipid metabolism in depressive-like macaques. These findings suggest that the gut microbiome may influence the onset of depressive behaviors by affecting peripheral and central glycerophospholipid metabolism, providing a new framework for understanding the role of the MGB axis in depression.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Enrico Ullmann, George Chrousos, Seth W. Perry, Ma-Li Wong, Julio Licinio, Stefan R. Bornstein, Olga Tseilikman, Maria Komelkova, Maxim S. Lapshin, Maryia Vasilyeva, Evgenii Zavjalov, Oleg Shevelev, Nikita Khotskin, Galina Koncevaya, Anna S. Khotskina, Mikhail Moshkin, Olga Cherkasova, Alexey Sarapultsev, Roman Ibragimov, Igor Kritsky, Joerg M. Fegert, Vadim Tseilikman, Rachel Yehuda
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Editorial Material
Biochemistry & Molecular Biology
Tarun Bastiampillai, Stephen Allison, Jeffrey C. L. Looi, Julio Licinio, Ma-Li Wong, Seth W. Perry
MOLECULAR PSYCHIATRY
(2020)
Article
Multidisciplinary Sciences
Jian Yang, Peng Zheng, Yifan Li, Jing Wu, Xunmin Tan, Jingjing Zhou, Zuoli Sun, Xu Chen, Guofu Zhang, Hanping Zhang, Yu Huang, Tingjia Chai, Jiajia Duan, Weiwei Liang, Bangmin Yin, Jianbo Lai, Tingting Huang, Yanli Du, Peifen Zhang, Jiajun Jiang, Caixi Xi, Lingling Wu, Jing Lu, Tingting Mou, Yi Xu, Seth W. Perry, Ma-Li Wong, Julio Licinio, Shaohua Hu, Gang Wang, Peng Xie
Article
Medicine, General & Internal
Charlotte Blacketer, Roger Parnis, Kyle B. Franke, Morganne Wagner, David Wang, Yiran Tan, Luke Oakden-Rayner, Steve Gallagher, Seth W. Perry, Julio Licinio, Ian Symonds, Josephine Thomas, Paul Duggan, Stephen Bacchi
Summary: This study conducted formative examinations and surveys in Australia, New Zealand, and the United States to evaluate the understanding of ML models among medical students and doctors. The majority of participants had difficulty in identifying weaknesses in model performance analysis, suggesting the need for further studies on educational interventions addressing ML topics.
INTERNAL MEDICINE JOURNAL
(2021)
Article
Virology
M. H. Raymonda, J. H. Ciesla, M. Monaghan, J. Leach, G. Asantewaa, L. A. Smorodintsev-Schiller, M. M. Lutz, X. L. Schafer, T. Takimoto, S. Dewhurst, J. Munger, I. S. Harris
Summary: A high-throughput screen revealed FDA-approved agents, including lapatinib, doramapimod, and 17-AAG, that can attenuate both OC43 and SARS-CoV-2 viral replication. Lapatinib demonstrated a significant inhibition of SARS-CoV-2 RNA replication by over 50,000-fold. Additionally, both lapatinib and doramapimod showed improved antiviral activity when combined with remdesivir.
Article
Psychiatry
Jing Wu, Tingjia Chai, Hanping Zhang, Yu Huang, Seth W. Perry, Yifan Li, Jiajia Duan, Xunmin Tan, Xi Hu, Yiyun Liu, Juncai Pu, Haiyang Wang, Jinlin Song, Xin Jin, Ping Ji, Peng Zheng, Peng Xie
Summary: This study investigated the impact of gut microbiota on the molecular mechanisms of depression using the Macaca fascicularis model. The researchers identified specific gut viruses and bacteria that can differentiate between depression-like monkeys and control monkeys. Moreover, lipidomic analysis revealed alterations in the abundance, carbon-chain length, and unsaturation degree of 1,2-diacylglyceride in the prefrontal cortex of depression-like monkeys. These changes were associated with the onset of negative emotional behaviors.
TRANSLATIONAL PSYCHIATRY
(2022)
Review
Public, Environmental & Occupational Health
Seth W. Perry, Jacob C. Rainey, Stephen Allison, Tarun Bastiampillai, Ma-Li Wong, Julio Licinio, Steven S. Sharfstein, Holly C. Wilcox
Summary: Suicide rates in the US show disparities based on age, sex, race/ethnicity, geography, and other factors. Untreated or unidentified depression and access to firearms are identified as major risk factors for suicide. Firearm suicides are increasing in rural areas, while suicides by falls decrease. To reduce suicide death disparities and achieve health equity, emphasis should be placed on policies and universal programs to reduce suicidal behaviors and improving strategies for depression and firearm prevention.
Article
Medicine, General & Internal
Antoinette Lam, Lydia Lam, Charlotte Blacketer, Roger Parnis, Kyle Franke, Morganne Wagner, David Wang, Yiran Tan, Lauren Oakden-Rayner, Steve Gallagher, Seth W. Perry, Julio Licinio, Ian Symonds, Josephine Thomas, Paul Duggan, Stephen Bacchi
Summary: This study investigates the use of machine learning in medical student evaluation and finds that bidirectional encoder representations are effective for professionalism question scoring. However, the classification accuracy for 3-mark professionalism questions is lower compared to clinical questions. Further research is needed to explore the role of machine learning in medical professionalism evaluation.
INTERNAL MEDICINE JOURNAL
(2022)
Article
Clinical Neurology
Yifan Li, Hanping Zhang, Peng Zheng, Jian Yang, Jing Wu, Yu Huang, Xi Hu, Xunmin Tan, Jiajia Duan, Tingjia Chai, Jingjing Zhou, Zuoli Sun, Min Liu, Jianbo Lai, Tingting Huang, Yanli Du, Peifen Zhang, Wenjuan Sun, Yun Ding, Chun Luo, Jianhua Zhao, Seth W. Perry, Ma-Li Wong, Julio Licinio, Shaohua Hu, Peng Xie, Gang Wang
Summary: This study explored the gender specificity of gut microbiome in patients with unipolar and bipolar depression disorder. Specific microbial changes were found in both disorders, and a gender-specific biomarker panel was identified with good diagnostic performance.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Yu Huang, Jing Wu, Hanping Zhang, Yifan Li, Lu Wen, Xunmin Tan, Ke Cheng, Yiyun Liu, Juncai Pu, Lanxiang Liu, Haiyang Wang, Wenxia Li, Seth W. Perry, Ma-Li Wong, Julio Licinio, Peng Zheng, Peng Xie
Summary: Clinical and animal studies have shown that disturbances in the gut microbiome can affect brain function and behaviors, possibly contributing to the development of brain diseases. This study used single-cell nucleus sequencing to examine specific transcriptomic changes in the prefrontal cortex and hippocampus of mice with different gut microbiome status. The absence of gut microbiota led to cell-specific transcriptomic changes, particularly in microglia. The gut microbiome was found to modulate the transformation of microglial subtypes, which may provide new insights into the pathogenesis of diseases like Alzheimer's disease and major depressive disorder.
MOLECULAR PSYCHIATRY
(2023)
Article
Psychology, Multidisciplinary
Taryn Lores, Michael Musker, Kathryn Collins, Anne Burke, Seth W. Perry, Ma-Li Wong, Julio Licinio