Article
Medicine, Research & Experimental
Sara Ayuso-Dolado, Gema M. Esteban-Ortega, Oscar G. Vidaurre, Margarita Diaz-Guerra
Summary: Postsynaptic density protein-95 (PSD-95) is critical for signaling complex assembly at excitatory synapses and interference of its processing by excitotoxicity could be a promising therapeutic target for stroke and other excitotoxicity-associated pathologies.
Article
Neurosciences
Kim Dore, Roberto Malinow
Summary: The study showed that NMDA receptors can signal through conformational change independently of ion flux, leading to long-term depression of synaptic transmission. PSD-95 overexpression was found to block agonist-induced conformational changes in the NMDAR intracellular domain and NMDAR-dependent, ion-flux independent LTD. This suggests that ion-flux independent LTD may be predominant in young animals due to lower levels of PSD-95 at synapses.
Review
Biochemistry & Molecular Biology
Lola Ugalde-Trivino, Margarita Diaz-Guerra
Summary: Recent research has shown that targeting PSD-95 may be an effective strategy for protecting neurons in cases of stroke. Two different therapeutic approaches using cell penetrating peptides have been developed and advanced to clinical stages. A third peptide has also been developed to interfere with PSD-95 cleavage, reducing neuronal death and improving outcomes in preclinical models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Anagh Sinha Ravi, Menglong Zeng, Xudong Chen, Gerardo Sandoval, Javier Diaz-Alonso, Mingjie Zhang, Roger A. Nicoll
Summary: Recent research suggests that the TARP/PSD-95 complex is an essential interaction underlying AMPAR trafficking and LTP. The interaction between PSD-95 and AMPAR auxiliary subunits TARPs can capture AMPARs and enhance synaptic transmission and LTP.
Article
Biochemistry & Molecular Biology
Roberta Giaccari, Francesco Marchesani, Carlotta Compari, Emilia Fisicaro, Andrea Mozzarelli, Barbara Campanini, Stefano Bettati, Stefano Bruno, Serena Faggiano
Summary: Human serine racemase (hSR) is an important enzyme in glutamatergic neurotransmission, and its activity is regulated by various factors, including its interaction with other protein partners. This study investigated the interaction between hSR and postsynaptic density protein 95 (PSD-95), and found that their binding is weak and may require the involvement of a third protein partner to stabilize it.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Zheng Shen, Daxiao Sun, Adriana Savastano, Sara Joana Varga, Maria-Sol Cima-Omori, Stefan Becker, Alf Honigmann, Markus Zweckstetter
Summary: Alzheimer's disease is characterized by progressive memory loss and cognitive impairment. A study found that the protein Tau, which is associated with cognitive dysfunction in Alzheimer's disease, can disrupt the formation and function of droplets in the postsynaptic density. This research provides insights into the molecular mechanisms underlying synaptic dysfunction in Alzheimer's disease.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Silvia Lores-Arnaiz, Analia G. Karadayian, Alicia Gutnisky, Jennifer Miranda, Georgina Rodriguez de Lores Arnaiz
Summary: Nitric oxide generation is closely related to the activity of certain proteins at synaptic sites. Administration of levocabastine in rats can alter the expression of synaptic proteins and mitochondrial function, ultimately affecting the functional interaction between different proteins and NO synthesis. Levocabastine-induced alterations in synaptic proteins and mitochondrial bioenergetics may play a significant role in the regulation of NO synthesis.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Anji Song, Gwang-Won Cho, Changjong Moon, Ilyong Park, Chul Ho Jang
Summary: The effect of resveratrol on tinnitus has not been reported. This study found that resveratrol attenuated salicylate-induced tinnitus in both in vitro and in vivo experiments. It reduced the expression of certain genes associated with tinnitus and showed potential as a therapeutic option.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Kara A. Lau, Xin Yang, Mengia S. Rioult-Pedotti, Stephen Tang, Mark Appleman, Jianan Zhang, Yuyang Tian, Caitlin Marino, Mudi Yao, Qin Jiang, Ayumi C. Tsuda, Yu-Wen Alvin Huang, Cong Cao, John Marshall
Summary: Angelman Syndrome (AS) is a severe cognitive disorder caused by loss of neuronal expression of the E3 ubiquitin ligase UBE3A. Researchers have found that a peptidomimetic compound called CN2097, which binds to the TrkB-associated scaffolding protein PSD-95, can restore synaptic plasticity and learning deficits in AS mice. CN2097 normalizes autophagy and restores synaptic protein levels, leading to improvements in cognitive and motor function.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Neurosciences
Anna Caly, Malgorzata A. Sliwinska, Magdalena Ziolkowska, Kacper Lukasiewicz, Roberto Pagano, Jakub M. Dzik, Katarzyna Kalita, Tytus Bernas, Michael G. Stewart, K. Peter Giese, Kasia Radwanska
Summary: A study using IntelliCage examined the behavioral processes supporting spatial choices of aged female mice living in a group, finding that old animals use behavioral strategies characterized by an increased tendency for perseverative visits and social interactions, resulting in a robust preference for the reward corner during the spatial choice task.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Gui-Mei Wu, Cai-Ping Du, Yan Xu
Summary: This study demonstrates that A beta oligomers induce tyrosine phosphorylation of PSD-95 through the activation of GluN2A and GluN2B-containing NMDA receptors, mediated by SrcPTKs.
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2023)
Review
Medicine, Research & Experimental
Zihuan Shen, Mi Xiang, Chen Chen, Fan Ding, Yuling Wang, Chang Shang, Laiyun Xin, Yang Zhang, Xiangning Cui
Summary: This article reviews the glutamate-mediated excitotoxicity mechanism in post-ischemic stroke damage, focusing on the pathological changes in glutamate release, reuptake, NMDAR, and cellular signaling pathways. It also discusses new treatment targets and potential neuroprotective drugs for ischemic stroke.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Yonghong Zhang, Xiaoqian Fang, Luis Ascota, Libo Li, Lili Guerra, Audrey Vega, Amanda Salinas, Andrea Gonzalez, Claudia Garza, Andrew Tsin, Johannes W. Hell, James B. Ames
Summary: Chemical synaptic transmission is a highly regulated process and imbalanced neurotransmitters can lead to impairments. PSD-95 plays a crucial role in synaptic development and maturation, and its interaction with zinc may influence its postsynaptic membrane association and palmitoylation.
Article
Biochemistry & Molecular Biology
Nicole Zarate, Taylor A. Intihar, Dahyun Yu, Jacob Sawyer, Wei Tsai, Maha Syed, Luke Carlson, Rocio Gomez-Pastor
Summary: PSD-95 levels are reduced in aging and neurodegenerative diseases like Huntington's disease, along with depletion of Heat Shock transcription Factor 1 (HSF1). HSF1 directly regulates PSD-95 expression, playing a crucial role in synaptic gene regulation with implications in synapse maintenance under both basal and pathological conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Emmanuel Prikas, Holly Ahel, Kristie Stefanoska, Prita Riana Asih, Alexander Volkerling, Lars M. Ittner, Arne Ittner
Summary: Tau protein, mainly found in neuronal axons, can also be localized in dendrites where it interacts with PSD-95 at post-synapses. The interaction between tau and PSD-95 in the GUK domain provides insights into the molecular details of their protein complex. Understanding these interactions can help regulate neurotoxic signaling at the molecular level.
BIOCHEMISTRY AND CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Vinod Kumar, John D. Lee, Elizabeth J. Coulson, Trent M. Woodruff
Summary: The blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) are specialized structures that limit molecule entry and maintain homeostasis within the central nervous system. This study developed and validated a quantitative method for assessing BBB and BSCB integrity using sodium fluorescein. The method revealed changes in permeability in models of neurodegenerative diseases and could contribute to understanding the role of these neuroprotective barriers in neurodegeneration processes.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Lidia Madrid, Javier Jimenez-Martin, Elizabeth J. Coulson, Dhanisha J. Jhaveri
Summary: The production and circuit integration of new neurons in the adult mammalian hippocampus are highly sensitive to neuronal activity, with acetylcholine playing a key role in regulating neurogenesis. Further research is needed to gain a deeper understanding of the mechanisms and translational potential of acetylcholine and its receptors in this process of cellular neuroplasticity.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yan Zhao, Elizabeth J. Coulson, Xingli Su, Junfeng Zhang, Baoyong Sha, Hao Xu, Yating Deng, Yulong Chen, Jian Cao, Yunpeng Wang, Shuang Wang
Summary: Major depression is a prevalent psychiatric illness with severe functional impairment and high suicide rate. Research has shown that specific proteins like 14-3-3 epsilon play a key role in regulating stress responses and depressive-like behaviors, providing potential therapeutic targets for treating major depression. Pharmacological stabilization of 14-3-3 epsilon, such as with FC-A, shows promise in precluding neuronal apoptotic signaling and relieving depressive symptoms.
Editorial Material
Neurosciences
Jacinta N. Conroy, Dhanisha J. Jhaveri, Elizabeth J. Coulson
Summary: The direct interaction between antidepressants and TrkB revealed in a recent study sheds light on synaptic remodeling mechanisms, potentially enhancing the development of improved antidepressant therapeutics.
Review
Biochemistry & Molecular Biology
Jacinta N. Conroy, Elizabeth J. Coulson
Summary: Neurotrophin signaling is crucial for normal nervous system development and function. Understanding the mechanism of high-affinity receptor generation will facilitate the development of pharmaceuticals for the treatment of nervous system disorders. Despite decades of research, the modulation mechanism of the high-affinity complex remains unclear.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Neurosciences
Jeremy Hunt, Elizabeth J. Coulson, Rajendram Rajnarayanan, Henrik Oster, Aleksandar Videnovic, Oliver Rawashdeh
Summary: The use of animal models is crucial for understanding the mechanisms of Parkinson's disease. This review examines the extent to which different mouse models accurately reflect the sleep and circadian abnormalities observed in Parkinson's disease.
MOLECULAR NEURODEGENERATION
(2022)
Article
Multidisciplinary Sciences
Wei-Yun Shen, Cong Luo, Plinio Reinaldo Hurtado, Xiao-Jing Liu, Ru-Yi Luo, Hui Li, Zhao-Lan Hu, Jun-Mei Xu, Elizabeth J. Coulson, Ming Zhao, Xin-Fu Zhou, Ru-Ping Dai
Summary: This study found that the inappropriate expansion of antibody-secreting cells (ASCs) in systemic lupus erythematosus (SLE) is associated with the signaling of brain-derived neurotrophic factor precursor (proBDNF) and its receptor p75(NTR). By inhibiting proBDNF, p75(NTR), or specifically knocking out p75(NTR) in CD19(+) B cells, lupus mice can be treated, reducing the production of autoantibodies and kidney injury.
Article
Behavioral Sciences
Madeline K. Ashton, Andre V. L. Rueda, Ada M. C. Ho, Noradibah Arina Binte M. Noor Aizin, Hansa Sharma, Peter R. Dodd, Alfreda Stadlin, Rosana Camarini
Summary: Male and female individuals demonstrate different tendencies in drug abuse, including alcohol. These variations lead to distinct psychological and neurological consequences, such as the likelihood of developing dependence. In cases of alcohol-use disorder, the extent and pattern of brain damage also differ depending on comorbid diseases. Using autopsy tissue, our study investigates the mRNA transcript expression in relation to genotype for two GABA(A) receptor subunit genes, revealing differences in expression between sexes, genotypes, and brain regions. The findings suggest that sex differences in individuals with GABRA6 and GABRA2 variants may contribute to variations in susceptibility to alcohol-use disorder and alcohol-induced cirrhosis.
GENES BRAIN AND BEHAVIOR
(2022)
Review
Psychiatry
Ella Pearson, Dan Siskind, Ruth E. Hubbard, Emily H. Gordon, Elizabeth J. Coulson, Nicola Warren
Summary: Emerging evidence suggests that individuals with severe mental illness (SMI) are at an increased risk of frailty. This systematic review examined the prevalence and correlates of frailty, as well as the efficacy of interventions, in this population. The findings indicate a high prevalence of frailty among individuals with SMI, with associations to physical comorbidity, cognitive deficits, falls, and mortality. However, further research is needed to develop appropriate interventions for frailty in this population.
JOURNAL OF PSYCHIATRIC RESEARCH
(2022)
Article
Health Policy & Services
Ella Pearson, Dan Siskind, Ruth Hubbard, Emily Gordon, Elizabeth Coulson, Urska Arnautovska, Nicola Warren
Summary: This study examines the prevalence and characteristics of frailty in individuals with treatment-resistant schizophrenia, revealing a high rate of frailty and a younger age of onset. Frailty is positively associated with age and severity of psychiatric illness. The findings suggest that routine frailty assessments can lead to appropriate interventions, potentially improving life expectancy and quality of life.
COMMUNITY MENTAL HEALTH JOURNAL
(2023)
Article
Geriatrics & Gerontology
Xiaoqing Alice Zhou, Grace Ngiam, Lei Qian, Kornraviya Sankorrakul, Elizabeth J. Coulson, Kai-Hsiang Chuang
Summary: Degeneration of cholinergic neurons in the basal forebrain (BF) is a contributing factor to cognitive impairment. However, the volume changes measured by structural MRI in the BF do not directly reflect the changes in cholinergic neurons.
NEUROBIOLOGY OF AGING
(2022)
Article
Multidisciplinary Sciences
Lei Qian, Oliver Rawashdeh, Leda Kasas, Michael R. Milne, Nicholas Garner, Kornraviya Sankorrakul, Nicola Marks, Matthew W. Dean, Pu Reum Kim, Aanchal Sharma, Mark C. Bellingham, Elizabeth J. Coulson
Summary: Sleep-disordered breathing is a risk factor for Alzheimer's disease. By modeling sleep disordered breathing in a mouse model of Alzheimer's disease, researchers found that some features of Alzheimer's disease were worsened. These findings suggest a signaling mechanism and a potential preventive measure for sleep-disordered breathing-induced pathologies.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ramon Martinez-Marmol, YeJin Chai, Jacinta N. Conroy, Zahra Khan, Seong-Min Hong, Seon Beom Kim, Rachel S. Gormal, Dae Hee Lee, Jae Kang Lee, Elizabeth J. Coulson, Mi Kyeong Lee, Sun Yeou Kim, Frederic A. Meunier
Summary: The traditional medicinal mushroom Hericium erinaceus enhances peripheral nerve regeneration through neurotrophic activity. We identified N-de phenylethyl isohericerin (NDPIH) and hericene A as biologically active compounds from this mushroom that promote neurite outgrowth in hippocampal neurons. NDPIH acts through a neurotrophic pathway independent of TrkB with ERK1/2 activation, while hericene A acts through a novel pan-neurotrophic signaling pathway, leading to improved cognitive performance in mice.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Geriatrics & Gerontology
Ying Xia, Paul Maruff, Vincent Dore, Pierrick Bourgeat, Simon M. Laws, Christopher Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Victor L. Villemagne, Christopher C. Rowe, Colin L. Masters, Elizabeth J. Coulson, Jurgen Fripp
Summary: Dysfunction of the cholinergic basal forebrain system and amyloid-beta deposition are early pathological features in Alzheimer's disease. This study found that Aβ is associated with volume loss in the BF and hippocampus, and the effect varies within BF subregions. The degeneration of BF subregions during early AD also shows distinctive characteristics.
NEUROBIOLOGY OF AGING
(2023)
Article
Neuroimaging
Ying Xia, Eamonn Eeles, Jurgen Fripp, Donna Pinsker, Paul Thomas, Melissa Latter, Vincent Dore, Amir Fazlollahi, Pierrick Bourgeat, Victor L. Villemagne, Elizabeth J. Coulson, Stephen Rose
Summary: The dysfunction of the cholinergic basal forebrain neurotransmitter system has been found to play an important role in cognitive decline and dementia. A study used a validated method to directly measure cholinergic terminal integrity and investigated its value for assessing cholinergic denervation in the cortex and associated cognitive deficits. The results showed that there was a significant global reduction of cholinergic terminal integrity in the cortex of participants with mild cognitive impairment compared to cognitively unimpaired controls. The study also found correlations between the cholinergic terminal integrity and brain volumes, but no association with amyloid-beta status. The findings suggest the potential of using this method for early detection of cholinergic dysfunction in dementia.
NEUROIMAGE-CLINICAL
(2022)