Review
Cell Biology
Norbert Weiss, Gerald W. Zamponi
Summary: Neuronal voltage-gated calcium channels play a crucial role in regulating calcium entry into nerve endings and neurotransmitter release. G protein-coupled receptors (GPCRs) not only modulate channel activity through second messengers, but also physically interact with calcium channels to regulate their function. Studying the regulation of calcium channels by classical opioid and nociceptin receptors is important for understanding neuronal functions and developing potential treatments for diseases.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Min-Ho Nam, Woojin Won, Kyung-Seok Han, C. Justin Lee
Summary: The mu-opioid receptor (MOR) is crucial for pain relief, reward, and euphoria. Recent research has discovered the presence of MOR in hippocampal astrocytes, shedding light on how astrocytic MOR participates in opioid signaling in the hippocampus. This novel mechanism involving astrocytic MOR plays a key role in hippocampus-dependent conditioned place preference.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Neurosciences
Huiping Ding, Mei-Chuan Ko
Summary: NHP models have been instrumental in opioid research for over five decades, offering more accurate conclusions in areas such as analgesia, abuse liability, and respiratory depression. Recent studies suggest that mixed mu opioid and nociceptin/orphanin FQ peptide receptor partial agonists may serve as safe, non-addictive analgesics.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Chemistry, Multidisciplinary
Ranit Lahmy, Harald Hubner, Maximilian F. Schmidt, Daniel Lachmann, Peter Gmeiner, Burkhard Konig
Summary: This study developed photoswitchable ligands that can activate or deactivate clinically relevant mu-opioid receptors using light, allowing for spatial and temporal control of biological activity in various biological investigations. These ligands, modeled after the known agonist fentanyl, can change geometry upon exposure to light and have different photophysical and biochemical properties, which could be valuable in further studying the functional significance of the mu-opioid receptor.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Review
Behavioral Sciences
Isabell M. Meier, Jack van Honk, Peter A. Bos, David Terburg
Summary: Research has shown that the mu-opioid system plays a crucial role in pain processing, addiction, social learning, bonding, and empathy, reinforcing socially affiliative or protective behavior in response to positive and negative social experiences. This system has long-term consequences for social behavior and health, with implications for stress, anxiety, depression, and attachment behaviors.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Multidisciplinary Sciences
Shijia Liu, Dong-Il Kim, Tae Gyu Oh, Gerald M. Pao, Jong-Hyun Kim, Richard D. Palmiter, Matthew R. Banghart, Kuo-Fen Lee, Ronald M. Evans, Sung Han
Summary: Neurons expressing the mu-opioid receptor within the lateral parabrachial nucleus play a crucial role in opioid-induced respiratory depression (OIRD). Chemogenetic modulation of these neurons can rescue respiratory rhythms and serve as a potential therapeutic target for treating OIRD in patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Keith M. Olson, Andrea L. Devereaux, Payal Chatterjee, Savanah L. Saldana-Shumaker, Amanda Shafer, Adam Plotkin, Ram Kandasamy, Alexander D. MacKerell, John R. Traynor, Christopher W. Cunningham
Summary: This study investigates the structure-activity relationships of benzylideneoxymorphone analogs in order to develop analgesics with reduced tolerance and side effects. One compound, nitro-BOM (NBOM), showed high-efficacy antinociception but also exhibited tolerance and toxicity upon repeated administration. Despite these issues, NBOM provides an important tool for understanding MOPr/DOPr pharmacology.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Derek W. Bartlett, Adam M. Gilbert
Summary: Targeted protein degradation has emerged as an exciting area for therapeutic development in the pharmaceutical industry. This review provides practical insights for understanding the pharmacokinetic and pharmacodynamic properties of protein degraders, and offers a roadmap for their translational development. By using quantitative mathematical frameworks and standard experimental assays, this review highlights the unique characteristics of protein degraders and their potential in drug development.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Biology
Benjamin Pillet, Alfonso Mendez-Godoy, Guillaume Murat, Sebastien Favre, Michael Stumpe, Laurent Falquet, Dieter Kressler
Summary: This study reveals the protective role of co-translational recognition on the degradation of Rpl3 and Rpl4 encoding genes, and identifies the regulatory function of dedicated chaperones in the assembly of nascent ribosomal proteins.
Article
Biochemistry & Molecular Biology
Yusuke Mizobuchi, Kanako Miyano, Sei Manabe, Eiko Uezono, Akane Komatsu, Yui Kuroda, Miki Nonaka, Yoshikazu Matsuoka, Tetsufumi Sato, Yasuhito Uezono, Hiroshi Morimatsu
Summary: This study investigated the effects of ketamine on opioid tolerance and its potential mechanisms. The results showed that ketamine improved acute desensitization and enhanced beta-arrestin recruitment elicited by fentanyl but not by morphine. These effects may involve modulation of GRK-mediated pathways.
Article
Chemistry, Medicinal
Taryn Bosquez-Berger, Jessica A. Gudorf, Charles P. Kuntz, Jacob A. Desmond, Jonathan P. Schlebach, Michael S. VanNieuwenhze, Alex Straiker
Summary: The US is facing a severe increase in fatal drug overdoses, with synthetic opioids like fentanyl causing 80% of deaths. Naloxone, the only antidote for opiate overdose, struggles against these synthetic opioids. A study has found that (-)-Cannabidiol ((-)-CBD), a candidate negative allosteric modulator (NAM) for the mu opioid receptor, shows potential as a more potent NAM than naloxone. The study suggests that CBD analogs have potential for the development of next-generation antidotes for opioid overdose.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Donghong Ju, Li Li, Youming Xie
Summary: Ribosomal proteins are regulated by cotranslational protein degradation, which does not require prior ubiquitylation. Cotranslational folding efficiency and expression level are critical factors determining cotranslational protein degradation of ribosomal proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Oncology
Douglas S. Micalizzi, Richard Y. Ebright, Daniel A. Haber, Shyamala Maheswaran
Summary: The deregulation of mRNA translation plays a crucial role in cancer cell spread and metastasis by influencing cellular states and responses to external stresses. This review focuses on the importance of altered translation in driving phenotypic changes and responses in metastatic progression, highlighting potential therapeutic opportunities to target metastatic tumor cells.
Review
Biochemistry & Molecular Biology
Ferenc Zador, Kornel Kiraly, Nariman Essmat, Mahmoud Al-Khrasani
Summary: This review summarizes recent data on the activation of mu opioid receptor (mu OR) by opioid agonists, including ligand recognition, signal transduction, and structural changes.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Behavioral Sciences
Luke A. Jelen, James M. Stone, Allan H. Young, Mitul A. Mehta
Summary: This article reviews the dysregulation of the opioid system in depression and the potential of pharmacological modulators of mu, delta, and kappa opioid receptors for the treatment of depression. The review presents evidence from animal and clinical studies supporting the dysregulation of the opioid system in depression, the modulation of behavioral processes and brain regions associated with depression by opioids, and the modulation of antidepressant responses by opioids. The review also evaluates clinical trials examining the safety and efficacy of opioidergic agents in depression and explores the involvement of the opioid system in the effects of other treatments, such as ketamine, that exert antidepressant effects through non-opioid actions. Furthermore, the review explores the neurochemical and molecular mechanisms underlying the therapeutic effects of opioid system engagement, providing a rationale for further investigation into this relevant target in depression treatment.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Neurosciences
Yan Wang, Yan-Hui Ge, Yan-Xia Wang, Ting Liu, Ping-Yee Law, Horace H. Loh, Hong-Zhuan Chen, Yu Qiu
CNS NEUROSCIENCE & THERAPEUTICS
(2015)
Article
Cell & Tissue Engineering
Chi Xu, Hui Zheng, Horace H. Loh, Ping-Yee Law
Article
Cell Biology
Kyu Young Song, Hack Sun Choi, Ping-Yee Law, Li-Na Wei, Horace H. Loh
JOURNAL OF CELLULAR PHYSIOLOGY
(2017)
Article
Pharmacology & Pharmacy
Jen-Hsin Kao, Man-Jun Gao, Pao-Pao Yang, Ping-Yee Law, Horace H. Loh, Pao-Luh Tao
BRITISH JOURNAL OF PHARMACOLOGY
(2015)
Review
Pathology
Yan Zhou, Kyu Young Song, Alessi Giubellino
AMERICAN JOURNAL OF PATHOLOGY
(2019)
Article
Oncology
Kyu Young Song, Sabina Desar, Thomas Pengo, Ryan Shanley, Alessio Giubellino
Article
Cell Biology
Fei Meng, Yuan Li, Hao Sun, Changpeng Li, Qian Li, Ping-Yee Law, Horace H. Loh, Lining Liang, Hui Zheng
Summary: The study showed that naloxone can promote the proliferation and differentiation of hippocampal neural stem cells, enhancing contextual learning and memory in mice. These effects were found to be receptor-independent but dependent on TET1.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Review
Cell Biology
Cherkaouia Kibaly, Jacob A. L. Alderete, Steven H. Liu, Hazem S. Nasef, Ping-Yee Law, Christopher J. Evans, Catherine M. Cahill
Summary: The abuse of opioid medications, particularly oxycodone, has become a significant crisis, leading to overdose deaths and addiction. Misuse of oxycodone is driven by its pharmacological properties, market strategies, and false claims of non-addictiveness, contributing to its high likability and abuse susceptibility. Understanding the unique pharmacology and marketing tactics of oxycodone is crucial in addressing the opioid epidemic and preventing further harm.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Article
Oncology
Alessio Giubellino, Andrew C. Nelson, Yuyu He, Sarah A. Munro, Kyu Young Song, Isabella C. Glitza Oliva, Carlos Torres-Cabala
Summary: Tumor heterogeneity is a characteristic of melanoma due to high mutation burden and immunogenicity. Understanding this can aid in developing predictive biomarkers and targeted therapies. In a case of melanoma, a dual phenotype was observed with shared mutations but distinct gene expression between different histologies.
PIGMENT CELL & MELANOMA RESEARCH
(2022)
Article
Genetics & Heredity
Yan Zhou, Andrew C. Nelson, Yuyu He, Sarah A. Munro, Kyu Young Song, Evidio Domingo-Musibay, Alessio Giubellino
Summary: BAP-1 inactivated melanocytic lesions exhibit distinct gene expression and mutational profiles, with genes involved in receptor protein kinase pathways gradually upregulated from nevus to melanoma. These lesions also show a gene enrichment in response to UV radiation, as well as upregulation of MAPK pathway-related genes and transcription factors related to melanomagenesis.
Article
Veterinary Sciences
Karen Koo, Arno Wuenschmann, Aaron Rendahl, Kyu Young Song, Colleen Forster, Amber Wolf-Ringwall, Antonella Borgatti, Alessio Giubellino
Summary: Analysis of canine melanoma tissue samples showed that MET receptor tyrosine kinase is expressed in these tumors, with a potential role in metastasis. However, further research is needed to fully understand its association with prognosis and treatment strategies in canine melanoma.
VETERINARY SCIENCES
(2023)
Article
Medicine, Research & Experimental
Lei Zhang, Cherkaouia Kibaly, Yu-Jun Wang, Chi Xu, Kyu Young Song, Patrick W. McGarrah, Horace H. Loh, Jing-Gen Liu, Ping-Yee Law
EMBO MOLECULAR MEDICINE
(2017)
Article
Medicine, Research & Experimental
Dong-Sun Lee, Ping-Yee Law, Wei Ln, Horace H. Loh, Kyu Young Song, Hack Sun Choi
BIOMEDICAL REPORTS
(2017)
Article
Cell Biology
Pao-Pao Yang, Geng-Chang Yeh, Eagle Yi-Kung Huang, Ping-Yee Law, Horace H. Loh, Pao-Luh Tao
JOURNAL OF BIOMEDICAL SCIENCE
(2015)