Physiologically relevant fluorescent assay for identification of 17 β‐hydroxysteroid dehydrogenase type 10 inhibitors
This study was focused on revalidation of the most potent HSD10 inhibitors derived from benzothiazolyl urea scaffold using fluorescent-based enzymatic assay with physiologically relevant substrates of 17β-oestradiol and allopreg nanolone. The oestradiol-based assay led to the identification of two nanomolar inhibitors (IC50 70 and 346 nM) differing from HSD10 hits revealed from the formerly used assay. Both identified inhibitors were found to be effective also in allopregnanolone-based assay with non-competitive or uncompetitive mode of action. In addition, both inhibitors were confirmed to penetrate the HEK293 cells a...
Source: Journal of Neurochemistry - July 18, 2023 Category: Neuroscience Authors: Monika Schmidt,
Michaela Vaskova,
Aneta Rotterova,
Pavlina Fiandova,
Marketa Miskerikova,
Lucie Zemanova,
Ondrej Benek,
Kamil Musilek Tags: ORIGINAL ARTICLE Source Type: research
Schwann cell ‐derived amphiregulin enhances nerve regeneration via supporting the proliferation and migration of Schwann cells and the elongation of axons
Peripheral nerve injury induces the elevation of growth factor amphiregulin (AREG) expression in Schwann cells. Up-regulated AREG supports the proliferation and migration of Schwann cells by activating ERK1/2 cascade, benefits the outgrowth of neurites and the elongation of injured axons, and thus may contribute to peripheral nerve repair and regeneration. Our results thus identify AREG as a promising therapeutic avenue towards peripheral nerve injury. AbstractPeripheral nerves have limited regeneration ability following nerve injury. Applying growth factors with neurotrophic roles is beneficial for accelerating peripheral...
Source: Journal of Neurochemistry - July 14, 2023 Category: Neuroscience Authors: Sailing Chen,
Qianqian Chen,
Xiaojiao Zhang,
Yinying Shen,
Xinyu Shi,
Xiu Dai,
Sheng Yi Tags: ORIGINAL ARTICLE Source Type: research
Serum microRNA ‐501‐3p is a potential diagnostic tool for detecting mild cognitive impairment: Ehime genome study
Blood –brain barrier (BBB) disruption is associated with cognitive decline, and miR-501-3p negatively regulates cerebral endothelial tight junction protein-1, leading to BBB disruption. The study aimed to investigate whether serum exosome miR-501-3p levels could serve as a clinical indicator for detecti ng mild cognitive impairment (MCI). The results showed that elevated expression of blood exosomal miR-501-3p is associated with the presence of MCI in human patients. Early detection of vascular injuries may reduce progressive dementia through the management of vascular risk factors. AbstractTight junction disruption and ...
Source: Journal of Neurochemistry - July 13, 2023 Category: Neuroscience Authors: Kensuke Toyama,
Joshua M. Spin,
Philip S. Tsao,
Koutatsu Maruyama,
Haruhiko Osawa,
Masaki Mogi,
Yasunori Takata Tags: ORIGINAL ARTICLE Source Type: research
IL ‐1β/IL‐1R1 signaling is involved in the propagation of α‐synuclein pathology of the gastrointestinal tract to the brain
Graphical abstract demonstrating IL-1 β/IL-1R1-dependent α-syn aggregation in the enteric nervous system and its propagation to brain. (1) The rotenone interacts with colon endothelial cells and (2) induces the activation of immune-inflammatory cells, including macrophages, release cytokines such as IL-1β. (3) IL-1 β binds to IL-1R1 on the surface of the ENS (Enteric nervous system) and (4) induces the accumulation of the α-syn, which further propagates to the DMV via the vagus nerve. (5) The aggregated α-syn from gastrointestinal tract into the DMV and to other brain parts as follows: ICP (inferior cerebellar pedun...
Source: Journal of Neurochemistry - July 12, 2023 Category: Neuroscience Authors: Bilal Muhammad,
Haiying Li,
Yunlu Gu,
Senlin Xue,
Yao Gao,
Zhou Xu,
Xiaoli Fang,
Haohan Ding,
Fang Wu,
Deqin Geng,
Haichen Niu Tags: ORIGINAL ARTICLE Source Type: research
Recent advances in cholinergic mechanisms as reactions to toxicity, stress, and neuroimmune insults
We reviewed the current advances in our understanding of the effects of a variety of stressors in order to connect acute poisoning with organophosphates, neurotoxicity, changes in microRNAs, and transfer RNA fragments with cholinergic signaling dysfunction. We highlighted recent studies of the chemical and molecular regulators of acetylcholine (ACh) signaling and the complexity of the mechanisms controlling cholinergic functioning in health and disease. AbstractThis review presents recent studies of the chemical and molecular regulators of acetylcholine (ACh) signaling and the complexity of the small molecule and RNA regul...
Source: Journal of Neurochemistry - July 11, 2023 Category: Neuroscience Authors: Zrinka Kovarik,
Gilli Moshitzky,
Nikolina Ma ček Hrvat,
Hermona Soreq Tags: REVIEW Source Type: research
A natural small molecule ‐mediated inhibition of alpha‐synuclein aggregation leads to neuroprotection in Caenorhabditis elegans
In this study, a small natural molecule shikonin has been explored for its anti-aggregation and neuroprotective activities. Shikonin significantly inhibited α-syn aggregation at equimolar and sub-stochiometric concentrations by stabilizing the monomers, increasing lag time and delaying elongation of α-syn fibrils. Also, inC. elegans PD models, shikonin showed neuroprotection and rescued neuronal degeneration by reducing α-syn aggregation, improving locomotor activity and preventing dopaminergic neuronal degeneration. The present study highlights the role of natural small molecules in the prevention of protein aggregatio...
Source: Journal of Neurochemistry - July 11, 2023 Category: Neuroscience Authors: Tulika Srivastava,
Divya Tyagi,
Siraj Fatima,
Malur Thirumalesh Vishnu Sathyan,
Ritu Raj,
Aniket Sharma,
Minal Chaturvedi,
Meetali Sinha,
Sonia Kumari Shishodia,
Dinesh Kumar,
Sandeep K. Sharma,
Jata Shankar,
Aruna Satish,
Smriti Priya Tags: ORIGINAL ARTICLE Source Type: research
JAG ‐1/Notch signaling axis in the spinal cord contributes to bone cancer pain in rats
Schematic showing that jagged1 (JAG-1)/Notch-1-mediated astrocyte-neuron interaction contributes to the maintenance of bone cancer-induced pain hypersensitivity: Bone cancer pain (BCP) induces up-regulation of JAG-1 expression in spinal astrocytes. Astrocyte JAG-1 regulates neuronal activation through the Notch signaling pathway and up-regulates hairy and enhancer of split homolog-1(Hes-1) expression by inducing the recruitment of Notch intracellular domain (NICD) to the RBP-J/CSL-binding site located within the Hes-1 promoter sequence, which contributes to BCP. AbstractNotch signal plays an important role in regulating ce...
Source: Journal of Neurochemistry - July 9, 2023 Category: Neuroscience Authors: Jie Fu,
Baoxia Zhao,
Ge Luo,
Huadong Ni,
Longsheng Xu,
Qiuli He,
Miao Xu,
Chengfei Xu,
Yahui Wang,
Chaobo Ni,
Ming Yao Tags: ORIGINAL ARTICLE Source Type: research
Mitochondrial calcium uniporter deficiency in dentate granule cells remodels neuronal metabolism and impairs reversal learning
The regulatory roles of the mitochondrial Ca2+ uniporter (MCU) on neuronal metabolism and function remain a puzzle. We found that MCU deficiency increases the net oxidative capacity of dentate granule cells in the hippocampus. The metabolic remodeling of these neurons also involves decreased levels of enzymes from lower glycolysis and diminished cellular antioxidant defenses. Ultimately, chronic MCU deficiency appears to lead to impaired cognitive flexibility in mice. Overall, our results reveal novel aspects of the regulation of neuronal physiology by MCU and provide evidence for its implication in learning and memory (Gr...
Source: Journal of Neurochemistry - July 7, 2023 Category: Neuroscience Authors: Hadyn M. Rose,
Beatriz Ferr án,
Rojina Ranjit,
Anthony M. Masingale,
Daniel B. Owen,
Stacy Hussong,
Michael T. Kinter,
Veronica Galvan,
Sreemathi Logan,
Carlos Manlio Díaz‐García Tags: ORIGINAL ARTICLE Source Type: research
Detection of early Alzheimer's disease ‐like molecular alterations in a mouse model expressing human ApoE4
We show that when compared to ApoE3-expressing mice, young ApoE4-expressing mice fed a high-fat diet were more prone to metabolic disturbances like those seen in insulin resistance. We also revealed that young ApoE4-expressing mice fed a high-fat diet show the differential expression of multiple genes, leading to alterations in downstream pathways related to neuron maintenance, insulin signaling, amyloid processing and clearance, and synaptic plasticity. These findings could aid in the identification of more tractable therapeutic targets for treating ApoE4-associated Alzheimer's disease. AbstractThe E4 allele of apolipopro...
Source: Journal of Neurochemistry - July 7, 2023 Category: Neuroscience Authors: A. Rai,
O. A. Ojiakor,
R. J. Rylett Tags: ORIGINAL ARTICLE Source Type: research
The following article for this Special Issue were previously published and can be found in its respective issue online:
Abstract:E3 ubiquitin ligase Nedd4-2 exerts neuroprotective effects during endoplasmic reticulum stress (Published in JNC 160.6 issue)https://onlinelibrary.wiley.com/doi/10.1111/jnc.15567 (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - July 7, 2023 Category: Neuroscience Tags: Correction Source Type: research
The following article for this Special Issue were previously published and can be found in its respective issue online:
Abstract:Amyloid processing in COVID-19-associated neurological syndromes (Published in JNC 161.2 issue)https://onlinelibrary.wiley.com/doi/10.1111/jnc.15585 (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - July 7, 2023 Category: Neuroscience Tags: Correction Source Type: research
Issue Information
Front coverThe life cycle of a protein encompasses its synthesis by the ribosome, chaperone-assisted folding, posttranslational modifications, subcellular
localization and, finally, protein turnover. Knowledge on the complexity of mechanisms driving protein homeostasis, or proteostasis, has grown considerably over the past decades, as well as the appreciation of the importance of proteostasis to brain functions, including cognition, mood, sleep, and appetite. Understanding the intricate mechanisms that act to preserve proteostasis may, therefore, result in novel treatments for neurodevelopmental and neurodegenerative disor...
Source: Journal of Neurochemistry - July 7, 2023 Category: Neuroscience Tags: ISSUE INFORMATION Source Type: research
Preface: Special issue “”
The special issue “Brain Proteostasis in Health and Disease” features both original and review articles written by specialists in the field of protein homeostasis. Deregulation of adequate proteostasis may contribute to brain diseases, including several neuropsychiatric and neurodegenerative conditions. Therefore , delineating the processes underlying protein synthesis, folding, stability, function, and degradation in brain cells is key to promoting brain function and identifying effective therapeutic options for neurological disorders. This special issue covers the roles of protein homeostasis in several me chanisms t...
Source: Journal of Neurochemistry - July 7, 2023 Category: Neuroscience Authors: Mychael V. Lourenco Tags: EDITORIAL Source Type: research
EDITOR SPOTLIGHT: Interview with Brain Proteostasis Special Issue Guest Editor Mychael Lourenco
Mychael Lourenco is an Assistant Professor of Neuroscience at the Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro. Research in his lab focusses on understanding the molecular mechanisms underlying cognitive impairment in neurodegeneration and his research on Alzheimer's disease has been recognized by many awards both in Brazil and internationally. He serves as a Reviews Editor for the Journal of Neurochemistry and led this special issue on Brain Proteostasis as a Guest Editor. Here we interviewed him to hear his thoughts on the future of neuroscience and on career development and tr...
Source: Journal of Neurochemistry - July 7, 2023 Category: Neuroscience Authors: JNC Editorial Office,
Kim H. Kwan,
Mychael V. Lourenco Tags: EDITORIAL Source Type: research
Preface: Special issue “Brain Proteostasis in Health and Disease”
The special issue “Brain Proteostasis in Health and Disease” features both original and review articles written by specialists in the field of protein homeostasis. Deregulation of adequate proteostasis may contribute to brain diseases, including several neuropsychiatric and neurodegenerative conditions. Therefore , delineating the processes underlying protein synthesis, folding, stability, function, and degradation in brain cells is key to promoting brain function and identifying effective therapeutic options for neurological disorders. This special issue covers the roles of protein homeostasis in several me chanisms t...
Source: Journal of Neurochemistry - July 6, 2023 Category: Neuroscience Authors: Mychael V. Lourenco Tags: EDITORIAL Source Type: research
