Article
Neurosciences
Gabrielle Zuniga, Bess Frost
Summary: Emerging evidence suggests that errors in RNA processing contribute to neurodegeneration. Neurons are particularly vulnerable to these errors, which can lead to accumulation of misprocessed RNA transcripts. Furthermore, the protein tau, implicated in Alzheimer's disease and related disorders, is also involved in deficits in RNA processing and clearance.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Neurosciences
Meng-Hua Zhou, Shao-Rui Chen, Li Wang, Yuying Huang, Meichun Deng, Jixiang Zhang, Jiyuan Zhang, Hong Chen, Jiusheng Yan, Hui-Lin Pan
Summary: The study identified the roles of PKC and alpha 2 delta-1 in controlling NMDAR activity, showing that co-expression of alpha 2 delta-1 significantly increased NMDAR activity, while PKC activation only increased receptor activity in cells co-expressing alpha 2 delta-1. Furthermore, phosphoproteomics analysis identified the phosphorylation sites responsible for NMDAR potentiation by PKC and alpha 2 delta-1.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
Yasir H. Qureshi, Diego E. Berman, Samuel E. Marsh, Ronald L. Klein, Vivek M. Patel, Sabrina Simoes, Suvarnambiga Kannan, Gregory A. Petsko, Beth Stevens, Scott A. Small
Summary: A study using a genetic mouse model reveals a causal link between neuronal retromer and late-onset Alzheimer's disease, and demonstrates that retromer can regulate pathological changes in both neuronal and microglial cells associated with the disease.
Article
Biochemistry & Molecular Biology
Sara R. Guerreiro, Marco R. Guimaraes, Joana M. Silva, Chrysoula Dioli, Anastasia Vamvaka-Iakovou, Raquel Sousa, Patricia Gomes, Anastasia Megalokonomou, Carlos Campos-Marques, Ana Margarida Cunha, Armando Almeida, Nuno Sousa, Hugo Leite-Almeida, Ioannis Sotiropoulos
Summary: Persistent pain has been suggested as a risk factor for dementia. This study investigates the molecular mechanisms underlying the relationship between chronic pain and dementia. The researchers found that chronic pain triggers Tau-related neuropathology, leading to neuronal atrophy and memory deficits. They also identified a potential mechanism involving the inhibition of autophagy and reduction of Tau degradation regulator Rab35. These findings highlight the importance of understanding how chronic pain contributes to memory loss and dementia through Tau-related pathways.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Hualing Peng, Jie Jia, Yisheng Lu, Hua Zheng
Summary: Isoflurane may treat schizophrenia by increasing the number of PV-positive GABAergic interneurons in the DG and repairing the abnormal NRG1-ErbB4 signaling, independent of PVI GABA release.
Article
Multidisciplinary Sciences
Fumiko Konishi, Tadasu Furusho, Yoshiyuki Soeda, Jun Yamauchi, Shoko Kobayashi, Masatoshi Ito, Takuma Araki, Sarasa Kogure, Akihiko Takashima, Susumu Takekoshi
Summary: The administration of Mucuna beans has been found to have a preventive effect on Alzheimer's disease development in triple-transgenic mice. It reduces the accumulation of extracellular amyloid-beta peptides and intracellular hyperphosphorylated tau protein, leading to improved cognitive function.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Biao Luo, Jian Chen, Gui-Feng Zhou, Xiao-Yong Xie, Jing Tang, Qi-Xin Wen, Li Song, Shi-Qi Xie, Yan Long, Guo-Jun Chen, Xiao-Tong Hu
Summary: Apicidin improves AD symptoms in APP/PS1 mice by regulating the expression of ADAM10, leading to a decrease in A beta levels rather than phosphorylation of tau.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Cell Biology
Mar Puigdellivol, Stefan Milde, Anna Vilalta, Tom O. J. Cockram, David H. Allendorf, Jeffrey Y. Lee, Jacob M. Dundee, Katryna Pampuscenko, Vilmante Borutaite, Hugh N. Nuthall, Jack H. Brelstaff, Maria Grazia Spillantini, Guy C. Brown
Summary: The P2Y(6) receptor plays a key role in mediating microglial phagocytosis of neurons induced by A beta and tau, leading to neuronal and memory loss. Knockout of this receptor could potentially be beneficial in the treatment of neurodegenerative diseases.
Article
Plant Sciences
Caixia Zang, Hui Liu, Junmei Shang, Hanyu Yang, Lu Wang, Chanjuan Sheng, Zihong Zhang, Xiuqi Bao, Yang Yu, Xinsheng Yao, Dan Zhang
Summary: The study demonstrates that GJ-4 improves cognitive deficits in APP/PS1 transgenic mice by reducing A beta levels, inhibiting tau protein phosphorylation, and suppressing neuroinflammatory responses. These findings provide a basis for further development of GJ-4 as a potential treatment for AD.
Article
Clinical Neurology
Antonio Valencia, Veronica L. Reinhart Bieber, Bekim Bajrami, Galina Marsh, Stefan Hamann, Ru Wei, Karen Ling, Frank Rigo, H. Moore Arnold, Olga Golonzhka, Heike Hering
Summary: Acetylation of tau protein is dysregulated in Alzheimer's Disease. Despite knocking down HDAC6 protein, there was no observed increase in tau acetylation or changes in tau phosphorylation or aggregation in PS19 mice, indicating that HDAC6 does not impact tau pathology in this model.
FRONTIERS IN NEUROLOGY
(2021)
Article
Pharmacology & Pharmacy
Bangfu Zhu, Tom Parsons, Wenche Stensen, John S. Mjoen Svendsen, Anders Fugelli, James J. L. Hodge
Summary: Alzheimer's disease, a common neurodegenerative disease with no cure, is more prevalent in Down syndrome patients due to potential genetic factors. Research has shown that targeting DYRK1A gene with medication can reduce neurodegeneration caused by AD and DS-related genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Bangfu Zhu, Tom Parsons, Wenche Stensen, John S. Mjoen Svendsen, Anders Fugelli, James J. L. Hodge
Summary: Alzheimer's disease (AD) is a common neurodegenerative disease with no effective treatments. People with Down syndrome (DS) have an increased risk of AD, and DYRK1A may be a potential therapeutic target. Through studying Drosophila models, it was found that the DYRK1A inhibitor PST-001 can improve the pathological processes caused by AD and DS-associated genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vivek Nilesh Shah, Julia Neumeier, Miguel Quevillon Huberdeau, Daniela M. Zeitler, Astrid Bruckmann, Gunter Meister, Martin J. Simard
Summary: The conserved serine/threonine kinases CK1A1 and CK2 regulate a phosphorylation cluster on the miRNA-specific AGO protein ALG-1, which is essential for miRISC-target RNA binding and silencing in Caenorhabditis elegans and humans.
Article
Biochemistry & Molecular Biology
Tushar Dubey, Preeti Kushwaha, H. V. Thulasiram, Madhura Chandrashekar, Subashchandrabose Chinnathambi
Summary: In this study, the ethanolic extract of Bacopa monnieri was found to inhibit Tau aggregation and rescue the viability of Tau-stressed cells. Bacopa monnieri reduced Tau aggregation in vitro and decreased ROS and caspase-3 activity in cells. It acted as an antioxidant and restored Nrf2 levels, reduced phospho-Tau load, and phosphorylation of GSK-3 beta in formaldehyde-stressed cells. Furthermore, it restored the NUP358 arrangement in cells, suggesting that Bacopa monnieri could be considered a promising formulation for Alzheimer's disease.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Editorial Material
Cell Biology
Mathieu Bourdenx, Evripidis Gavathiotis, Ana Maria Cuervo
Summary: Different types of autophagy have distinct contributions to maintenance of cellular proteostasis, with chaperone-mediated autophagy (CMA) playing a key role in preserving the metastable proteome. Loss of CMA exacerbates proteotoxicity in neurodegenerative conditions like Alzheimer's disease, while pharmacological enhancement of CMA shows promise in improving behavior and pathology in AD mouse models.
Article
Chemistry, Multidisciplinary
Filip Hasecke, Chamani Niyangoda, Gustavo Borjas, Jianjun Pan, Garrett Matthews, Martin Muschol, Wolfgang Hoyer
Summary: The study found that in the assembly of A beta and lysozyme, protofibrils bind to the lateral surfaces of amyloid fibrils, inhibiting the self-proliferation of amyloid fibrils. This suggests that metastable oligomers counteract the replacement by amyloid fibrils through competing for monomers and blocking secondary nucleation sites.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Shon A. Koren, Matthew J. Hamm, Ryan Cloyd, Sarah N. Fontaine, Emad Chishti, Chiara Lanzillotta, Jennifer Rodriguez-Rivera, Alexandria Ingram, Michelle Bell, Sara M. Galvis-Escobar, Nicholas Zulia, Fabio Di Domenico, Duc Duong, Nicholas T. Seyfried, David Powell, Moriel Vandsburger, Tal Frolinger, Anika M. S. Hartz, John Koren, Jeffrey M. Axten, Nicholas J. Laping, Jose F. Abisambra
Summary: Tauopathies are a group of disorders involving neurodegeneration and cognitive decline, with limited therapeutic options due to lack of understanding of molecular mechanisms. Treating early stage tau transgenic mice with a multi-target kinase inhibitor improved brain atrophy and cognitive function, despite unchanged levels of hyperphosphorylated tau. Proteomics data identified potential therapeutic targets for tauopathy treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Dylan A. Reid, Patrick J. Reed, Johannes C. M. Schlachetzki, Ioana I. Nitulescu, Grace Chou, Enoch C. Tsui, Jeffrey R. Jones, Sahaana Chandran, Ake T. Lu, Claire A. McClain, Jean H. Ooi, Tzu-Wen Wang, Addison J. Lana, Sara B. Linker, Anthony S. Ricciardulli, Shong Lau, Simon T. Schafer, Steve Horvath, Jesse R. Dixon, Nasun Hah, Christopher K. Glass, Fred H. Gage
Summary: Neurons, as the longest-lived cells in our bodies, lack DNA replication and rely on a limited repertoire of DNA repair mechanisms to maintain genome fidelity. Research has found that DNA repair in neurons is enriched at well-defined hotspots, which are associated with evolutionarily conserved elements of the human genome. These findings provide insights into the protection of genome integrity in the aging and disease of the nervous system.
Correction
Neurosciences
Marangelie Criado-Marrero, Niat T. Gebru, Danielle M. Blazier, Lauren A. Gould, Jeremy D. Baker, David Beaulieu-Abdelahad, Laura J. Blair
Summary: An amendment to the paper has been published and is accessible through the original article.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Neurosciences
Marangelie Criado-Marrero, Niat T. Gebru, Danielle M. Blazier, Lauren A. Gould, Jeremy D. Baker, David Beaulieu-Abdelahad, Laura J. Blair
Summary: The study found that overexpression of molecular chaperones FKBP52 and Aha1 can promote the accumulation of tau protein in the brains of aged wild-type mice, leading to cognitive and pathological changes. Overexpression of FKBP52 impaired spatial reversal learning, while overexpression of Aha1 impaired associative learning.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Cell Biology
Pradoldej Sompol, Jenna L. Gollihue, Susan D. Kraner, Irina A. Artiushin, Ryan A. Cloyd, Emad A. Chishti, Shon A. Koren, Grant K. Nation, Jose F. Abisambra, Orsolya Huzian, Lajos I. Nagy, Miklos Santha, Laszlo Hackler, Laszlo G. Puskas, Christopher M. Norris
Summary: Inhibition of the protein phosphatase calcineurin (CN) can improve pathophysiological and cognitive changes in aging rodents and mice with aging-related Alzheimer's disease (AD)-like pathology. A newly developed neuroprotective hydroxyquinoline derivative (Q134R) that suppresses NFAT signaling, without inhibiting CN activity, shows promising results in improving cognitive performance and potentially increasing longevity in mice. These findings suggest that Q134R could be a valuable drug for treating AD and aging-related disorders.
Article
Endocrinology & Metabolism
Lisa Y. Lawson, Michael D. Brodt, Nicole Migotsky, Christopher J. Chermside-Scabbo, Ramya Palaniappan, Matthew J. Silva
Summary: The secretion of Wnt ligands is essential for adult bone homeostasis, and inhibiting their secretion results in decreased bone formation and increased resorption. Additionally, osteoblast-derived Wnts play a crucial role in mediating the bone anabolic response to tibial loading.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Santiago Rodriguez Ospina, Danielle M. Blazier, Marangelie Criado-Marrero, Lauren A. Gould, Niat T. Gebru, David Beaulieu-Abdelahad, Xinming Wang, Elizabeth Remily-Wood, Dale Chaput, Stanley Stevens, Vladimir N. Uversky, Paula C. Bickford, Chad A. Dickey, Laura J. Blair
Summary: The study found that overexpression of Hsp22 can protect synaptic plasticity and cognition in tauopathic brains, without significantly altering tau phosphorylation levels. Mass spectrometry analysis revealed that Hsp22 overexpression in neurons promotes synaptic plasticity by regulating canonical pathways and upstream regulators related to potential AD markers and synaptogenesis regulators.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Abraham Lopez, Vinay Dahiya, Florent Delhommel, Lee Freiburger, Ralf Stehle, Sam Asami, Daniel Rutz, Laura Blair, Johannes Buchner, Michael Sattler
Summary: Hsp90, a molecular chaperone, forms a key intermediate state induced by ATP binding, with rotations in the N-terminal domain affecting distant client sites. Client-specific interactions select and enhance the rotated state of Hsp90, promoting closing of the full-length dimer. The co-chaperone p23 shifts Hsp90 towards the closed state, enhancing client interaction and processing.
Review
Neurosciences
Ariel Walker, Ben Chapin, Jose Abisambra, Steven T. DeKosky
Summary: This literature review investigated whether a single moderate to severe head injury leads to long-term development of tauopathy. The results of most human and animal studies suggest that a single moderate to severe head injury is associated with greater chronic development of tauopathy, but caution is needed due to limitations in the studies.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Lisa Y. Lawson, Nicole Migotsky, Christopher J. Chermside-Scabbo, John T. Shuster, Kyu Sang Joeng, Roberto Civitelli, Brendan Lee, Matthew J. Silva
Summary: Mechanical loading stimulates bone formation, and the Wnt signaling pathway plays a crucial role in the skeletal response to loading. Specifically, Wnt1 mediates the mechano-adaptive response to loading.
Article
Biochemistry & Molecular Biology
Shannon E. Hill, Abigail R. Esquivel, Santiago Rodriguez Ospina, Lauren M. Rahal, Chad A. Dickey, Laura J. Blair
Summary: Tauopathies, such as Alzheimer's disease, are characterized by the misfolding and accumulation of the protein tau. This study shows that cyclophilins, a group of chaperones, can prevent tau aggregation and reduce insoluble tau accumulation in cells. PPIC shows the most potential in mitigating tau seeding and accumulation.
Article
Multidisciplinary Sciences
Lulu Jiang, Pijush Chakraborty, Lushuang Zhang, Melissa Wong, Shannon E. Hill, Chelsea Joy Webber, Jenna Libera, Laura J. Blair, Benjamin Wolozin, Markus Zweckstetter
Summary: Alzheimer's disease and related tauopathies are characterized by misfolding and aggregation of the protein tau. This study demonstrates that the immunophilin FKBP12 regulates neuronal resilience by acting as a chaperone for monomeric tau. The study identifies the molecular factors involved in FKBP12's binding to tau and its influence on tau-induced neurotoxicity.
Review
Biochemistry & Molecular Biology
Yanan Zhu, Lauren Gandy, Fuming Zhang, Jian Liu, Chunyu Wang, Laura J. Blair, Robert J. Linhardt, Lianchun Wang
Summary: This review summarizes the current understanding of the functions and modulated molecular pathways of heparan sulfate proteoglycans in tauopathies, as well as the potential of targeting heparan sulfate proteoglycan-tau interaction as a novel therapeutic option.
Review
Biochemistry & Molecular Biology
Niat T. Gebru, Shannon E. Hill, Laura J. Blair
Summary: FK506 binding protein 51 (FKBP51) is a molecular chaperone involved in stress response and various biological processes. Genetic and epigenetic alterations in the FKBP5 gene are associated with neuropsychiatric disorders. Animal models, such as mouse models, have played a crucial role in understanding the function of FKBP51. This review examines different mouse models of FKBP5, discussing their generation, observations, and potential implications for stress-related disorders.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)