Article
Biochemistry & Molecular Biology
Zhang Huiliang, Yang Mengzhe, Wang Xiaochuan, Wei Hui, Du Min, Wang Mengqi, Wang Jianzhi, Chen Zhongshan, Peng Caixia, Liu Rong
Summary: High levels of zinc in AD brains induce harmful A1-type reactive astrogliosis, which promotes synaptic degeneration. Zinc activates ERK and JAK2 to phosphorylate Stat3, leading to astrogliosis.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ying Zhou, Xiaoyuan Liu, Shuqing Ma, Nan Zhang, Dichen Yang, Ling Wang, Simin Ye, Qiongying Zhang, Jing Ruan, Jun Ma, Shiyi Wang, Nan Jiang, Zongyuan Zhao, Shujue Zhao, Chenfei Zheng, Xiaofang Fan, Yongsheng Gong, Mahaman Yacoubou Abdoul Razak, Wenting Hu, Jingye Pan, Xiaochuan Wang, Junming Fan, Jianmin Li, Rong Liu, Yangping Shentu
Summary: This study found that the activation of DNA damage-related Checkpoint kinase 1 (ChK1) in Alzheimer's disease leads to overexpression of CIP2A, which in turn causes reactive astrogliosis, neurodegeneration, and exacerbation of AD.
Article
Immunology
Ivan Ballasch, Esther Garcia-Garcia, Cristina Vila, Anna Perez-Gonzalez, Anna Sancho-Balsells, Jessica Fernandez, David Soto, Mar Puigdellivol, Xavier Gasull, Jordi Alberch, Manuel J. Rodriguez, Josep M. Canals, Albert Giralt
Summary: In the last two decades, microglia have been recognized as important contributors to neurological disorders, not only through their immunological functions, but also through their ability to modulate synaptic and neural activity. The Ikzf1 gene, which plays crucial roles in regulating the function of circulating monocytes and lymphocytes, was found to be specifically expressed in adult microglia in the brain. Studies using Ikzf1 deficient mice revealed spatial learning deficits, impaired hippocampal function, and altered microglial morphology, suggesting that Ikzf1 is involved in microglial state and function. Furthermore, altered levels of Ikzf1 were observed in neurological disorder models and Alzheimer's disease patients, indicating its potential role in disease pathology.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Environmental Sciences
Yiping Yang, Jie Zhang, Xiaobo Yang, Zhiying Li, Jian Wang, Cailing Lu, Aruo Nan, Yunfeng Zou
Summary: The study revealed that excessive exposure to manganese inhibits the expression and activity of APP and α-secretase, leading to cognitive impairment, while showing no significant effect on β-secretase.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Cell Biology
Aina Badia-Soteras, Janneke de Vries, Werner Dykstra, Laus M. Broersen, Jan Martin Verkuyl, August B. Smit, Mark H. G. Verheijen
Summary: Astrocytes are specialized glial cells that respond to central nervous system insults through reactive astrogliosis. Fortasyn Connect (FC) has shown promising effects in maintaining neuronal function and cognitive performance in early-stage Alzheimer's disease. Studies suggest that FC may reduce astrocyte reactivity by promoting neuronal survival and synaptogenesis, but the underlying mechanism is still unclear.
Review
Physiology
Alexei Verkhratsky, Marcus Augusto-Oliveira, Augustas Pivoriunas, Alexander Popov, Alexey Brazhe, Alexey Semyanov
Summary: Astroglia undergo morphological and functional changes with aging, leading to a decline in various functions in the central nervous system. Lifestyle interventions can influence and improve the morphology and function of astroglia, playing a crucial role in cognitive longevity.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chandramouli Natarajan, Charles Cook, Karthik Ramaswamy, Balaji Krishnan
Summary: Attenuating PLD1 expression has neurotherapeutic implications in tauopathies, as it can alleviate synaptic dysfunction and memory deficits. In mouse models, the use of PLD1 inhibitors improved cognitive function and preserved synaptic morphology, suggesting potential clinical applications for Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Gabriela Bortolanca Chiarotto, Luciana Politti Cartarozzi, Matheus Perez, Ana Laura Midori Rossi Tomiyama, Mateus Vidigal de Castro, Adriana S. S. Duarte, Angela Cristina Malheiros Luzo, Alexandre Leite Rodrigues de Oliveira
Summary: This study confirms the therapeutic potential of human mesenchymal stem cells (hMSCs) from adipose tissue in SOD1G93A transgenic mice. Treatment during the asymptomatic phase resulted in increased neuronal survival and reduced neurodegeneration.
BRAIN RESEARCH BULLETIN
(2022)
Article
Immunology
Dandan Wang, Yewei Wang, Yan Chen, Lingfang Yu, Zenan Wu, Ruimei Liu, Juanjuan Ren, Xinyu Fang, Chen Zhang
Summary: This study aimed to compare the differences in cognitive functioning and inflammatory cytokine levels among different types of schizophrenia patients and healthy controls. The results showed that deficit schizophrenia patients had worse cognitive performance and higher levels of certain inflammatory cytokines compared to nondeficit schizophrenia patients and healthy controls. These findings suggest that deficit syndrome may be an independent endophenotype of schizophrenia with unique immune-inflammatory features.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Pavan Thapak, Zhe Ying, Victoria Palafox-Sanchez, Guanglin Zhang, Xia Yang, Fernando Gomez-Pinilla
Summary: Traumatic brain injury (TBI) impairs cellular energy demand, compromising neuronal function and plasticity. This study demonstrates that the mitochondrial activator humanin (HN) can counteract the reduction in mitochondrial bioenergetics caused by TBI, restore memory function and synaptic protein levels, and suppress inflammation and astrocyte proliferation. HN plays an integral role in normalizing fundamental aspects of TBI pathology.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Victor James Drew, Mincheol Park, Tae Kim
Summary: This study examined the relationship between sleep disturbances and regional neuron and astrocyte pathologies in Alzheimer's disease (AD). The findings showed that 5XFAD mice demonstrated reduced NREM and REM sleep duration and bout counts, as well as decreased theta EEG power frequency during REM sleep. Sleep disturbances were correlated with the number and ratio of GFAP-positive astrocytes in sleep-promoting brain regions. This study reveals the link between neurotoxic reactive astrogliosis and sleep disturbances in AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Leandro Castaneyra-Ruiz, Ibrahim Gonzalez-Marrero, Luis G. Hernandez-Abad, Seunghyun Lee, Agustin Castaneyra-Perdomo, Michael Muhonen
Summary: This manuscript is a focused review of the current research landscape on AQP4 as a possible biomarker for gliogenesis and its influence in pediatric hydrocephalus, emphasizing reactive astrogliosis. The goal is to understand brain development under hydrocephalic and normal physiologic conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
David Pamies, Chiara Sartori, Domitille Schvartz, Victor Gonzalez-Ruiz, Luc Pellerin, Carolina Nunes, Denise Tavel, Vanille Maillard, Julien Boccard, Serge Rudaz, Jean-Charles Sanchez, Marie-Gabrielle Zurich
Summary: This study aimed to explore the metabolic changes occurring in activated human astrocytes. Results showed that activated astrocytes exhibited significant changes in inflammation response, cytoskeleton, and energy metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Physiology
David S. Bouvier, Sonja Fixemer, Tony Heurtaux, Felicia Jeannelle, Katrin B. M. Frauenknecht, Michel Mittelbronn
Summary: Astrocytes play multiple roles in the central nervous system, but in age-related neurodegenerative diseases, they may exhibit neurotoxic phenotypes that contribute to disease progression. Chronic inflammation, oxidative stress, impaired phagocytosis, and altered physiological roles are the main manifestations of astrocytic toxicity. However, the involvement of astrocytes in brain deterioration in patients with neurodegenerative diseases is still controversial due to overlapping pathologies and technical challenges in studying human brain samples. This review provides an overview of astrocyte neurotoxicity from in vitro findings to animal models and patient-related research, and discusses the role of aging in astrocytes and potential therapeutic strategies.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fanyu Meng, Jiafeng Fu, Lin Zhang, Mengqing Guo, Pengwei Zhuang, Qingsheng Yin, Yanjun Zhang
Summary: This review systematically summarizes the effects and mechanisms of diabetes on brain astrocytes, highlighting the contribution of reactive astrogliosis to diabetic cognitive impairment (DCI). Reactive astrogliosis contributes to DCI by increasing blood-brain barrier permeability, impairing glymphatic system function, promoting neuroinflammation, disrupting cell communication, and dysregulating cholesterol metabolism. Targeting astrocytes offers potential therapeutic strategies for treating DCI.
NEUROCHEMISTRY INTERNATIONAL
(2023)
Article
Oncology
Eleonora Makela, Karolina Pavic, Taru Varila, Urpu Salmenniemi, Eliisa Loyttyniemi, Srikar G. Nagelli, Tea Ammunet, Veli-Matti Kahari, Richard E. Clark, Laura L. Elo, Venkata Kumari Bachanaboyina, Claire M. Lucas, Maija Itala-Remes, Jukka Westermarck
Summary: A novel variant of the oncoprotein CIP2A, named NOCIVA, was discovered and found to be clinically relevant in predicting tyrosine kinase inhibitor therapy resistance in myeloid leukemias.
CLINICAL CANCER RESEARCH
(2021)
Article
Otorhinolaryngology
J. Routila, I Leivo, H. Minn, J. Westermarck, Sami Ventela
Summary: Population validation is crucial for improving the applicability of results to real-life situations in HNSCC studies. Controlling bias in retrospective studies, especially in the heterogeneous tumor environment of HNSCC, is essential for identifying biomarkers for clinical practice. Simple prognostic examination alone may not be sufficient for this purpose.
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ying Zhou, Xiaoyuan Liu, Shuqing Ma, Nan Zhang, Dichen Yang, Ling Wang, Simin Ye, Qiongying Zhang, Jing Ruan, Jun Ma, Shiyi Wang, Nan Jiang, Zongyuan Zhao, Shujue Zhao, Chenfei Zheng, Xiaofang Fan, Yongsheng Gong, Mahaman Yacoubou Abdoul Razak, Wenting Hu, Jingye Pan, Xiaochuan Wang, Junming Fan, Jianmin Li, Rong Liu, Yangping Shentu
Summary: This study found that the activation of DNA damage-related Checkpoint kinase 1 (ChK1) in Alzheimer's disease leads to overexpression of CIP2A, which in turn causes reactive astrogliosis, neurodegeneration, and exacerbation of AD.
Article
Clinical Neurology
Wenting Hu, Zhuoqun Wang, Huiliang Zhang, Yacoubou Abdoul Razak Mahaman, Fang Huang, Dongli Meng, Ying Zhou, Shiyi Wang, Nan Jiang, Jing Xiong, Jukka Westermarck, Youming Lu, Jianzhi Wang, Xiaochuan Wang, Yangping Shentu, Rong Liu
Summary: This study reveals that DNA damage-induced Chk1 activation promotes the development of Alzheimer's disease through CIP2A-mediated tau and APP hyperphosphorylation and cognitive dysfunction, highlighting the therapeutic potential of Chk1 inhibitors in AD.
Article
Oncology
Johannes Routila, Xi Qiao, Jere Weltner, Juha K. Rantala, Timo Carpen, Jaana Hagstrom, Antti Makitie, Ilmo Leivo, Miia Ruuskanen, Jenni Soderlund, Marjut Rintala, Sakari Hietanen, Heikki Irjala, Heikki Minn, Jukka Westermarck, Sami Ventela
Summary: This study identifies OCT4 as a potential biomarker to predict the therapeutic effect of treatment for head and neck squamous cell carcinoma (HNSCC). OCT4 expression in HNSCC tumors is associated with radioresistance, but combination therapy with cisplatin can overcome this resistance. The results of the study are validated using multiple independent patient cohorts.
Article
Multidisciplinary Sciences
Oxana Denisova, Joni Merisaari, Amanpreet Kaur, Laxman Yetukuri, Mikael Jumppanen, Carina Von Schantz-Fant, Michael Ohlmeyer, Krister Wennerberg, Tero Aittokallio, Mikko Taipale, Jukka Westermarck
Summary: Therapeutic resistance to kinase inhibitors, particularly in glioblastoma, is a major challenge in cancer treatment. Researchers have developed an actionable targets of multi-kinase inhibitors (AToMI) strategy to identify target kinases involved in the therapeutic effects of multi-kinase inhibitors. Using this strategy, they successfully characterized AKT and mitochondrial pyruvate dehydrogenase kinase PDK1 and PDK4 as target kinases of staurosporine derivatives that synergized with PP2A activation in glioblastoma cells.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Hui-Liang Zhang, Xiao-Chuan Wang, Rong Liu
Summary: Zinc is crucial for human growth and development, particularly in regulating the mechanisms of neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Wen-Ting Hu, Zhen-Yu Liuyang, Yuan Tian, Jia-Wei Liang, Xiao-Lin Zhang, Hui-Liang Zhang, Guan Wang, Yuda Huo, Yang-Ping Shentu, Jian-Zhi Wang, Xiao-Chuan Wang, You-Ming Lu, Jukka Westermarck, Heng-Ye Man, Rong Liu
Summary: This study discovers a novel mechanism in which CIP2A deficiency promotes depression through the regulation of PP2A-AKT signaling and dendritic arborization. The study also finds decreased expression of CIP2A in a mouse model of chronic unpredictable mild stress (CUMS) and in patients with major depressive disorder (MDD).
Article
Cell Biology
Umar Butt, Meraj H. Khan, Jeroen Pouwels, Jukka Westermarck
Summary: This study identifies the role of SHARPIN phosphorylation in cellular processes and cancer progression, with a specific focus on the S146 phosphorylation and its regulation of the ARP2/3 complex interaction, promoting cancer cell invasion.
JOURNAL OF CELL SCIENCE
(2022)
Article
Oncology
Anna Aakula, Aleksi Isomursu, Christian Rupp, Andrew Erickson, Nikhil Gupta, Otto Kauko, Pragya Shah, Artur Padzik, Yuba Raj Pokharel, Amanpreet Kaur, Song-Ping Li, Lloyd Trotman, Pekka Taimen, Antti Rannikko, Jan Lammerding, Ilkka Paatero, Tuomas Mirtti, Johanna Ivaska, Jukka Westermarck
Summary: This study found that prostate cancer tumors with concomitant inhibition of PP2A and PTEN are particularly aggressive, with low patient survival rates. Overexpression of PME-1 inhibits anoikis in PTEN-deficient prostate cancer cells. The results suggest that PME-1 may be a candidate biomarker for particularly aggressive PTEN-deficient prostate cancer.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Jukka Westermarck
Summary: Targeted therapies are commonly used in cancer treatment, but their effectiveness is limited by acquired drug resistance. Recent studies have highlighted the role of mitochondrial mechanisms in cancer cell sensitivity to targeted therapies, leading to the development of triplet therapies that target vulnerabilities in cancer cells, including the mitochondria. These triplet therapies show promising preclinical effects in overcoming drug resistance, but challenges in clinical translation need to be addressed.
MOLECULAR ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Karolina Pavic, Nikhil Gupta, Judit Domenech Omella, Rita Derua, Anna Aakula, Riikka Huhtaniemi, Juha A. Maatta, Nico Hofflin, Juha Okkeri, Zhizhi Wang, Otto Kauko, Roosa Varjus, Henrik Honkanen, Daniel Abankwa, Maja Kohn, Vesa P. Hytonen, Wenqing Xu, Jakob Nilsson, Rebecca Page, Veerle Janssens, Alexander Leitner, Jukka Westermarck
Summary: This study reveals the molecular level details and structural mechanisms of PP2A-B56 alpha inhibition by the oncoprotein CIP2A. CIP2A displaces the PP2A-A subunit and forms a pseudotrimer, blocking the B56 alpha substrate binding site and stabilizing CIP2A protein.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Anna Aakula, Mukund Sharma, Francesco Tabaro, Reetta Natkin, Jesse Kamila, Henrik Honkanen, Matthieu Schapira, Cheryl Arrowsmith, Matti Nykter, Jukka Westermarck
Summary: RAS-mediated human cell transformation requires inhibition of PP2A, and the co-regulated phosphosites on proteins involved in epigenetic gene regulation were discovered in this study. RAS and PP2A co-regulate phosphorylation sites on HDAC1/2, KDM1A, MTA1/2, RNF168, and TP53BP1. The study validates the regulation of HDAC1/2 chromatin recruitment, RNF168-TP53BP1 interaction, and gene expression by RAS and PP2A. This work provides insights into the convergence of RAS and PP2A in cancer.
LIFE SCIENCE ALLIANCE
(2023)
Meeting Abstract
Oncology
Mukund Sharma, Anna Aakula, Francesco Tabaro, Karolina Pavic, Riikka Huhtaniemi, Matti Nykter, Jukka Westermarck
Article
Geriatrics & Gerontology
Sarah N. Kraeutner, Cristina Rubino, Jennifer K. Ferris, Shie Rinat, Lauren Penko, Larissa Chiu, Brian Greeley, Christina B. Jones, Beverley C. Larssen, Lara A. Boyd
Summary: This study examined the age-related changes in brain function and baseline brain structure that support motor skill acquisition. The findings showed that older adults experienced decreases in functional connectivity during motor skill acquisition, while younger adults experienced increases. Additionally, regardless of age group, lower baseline microstructure in a frontoparietal tract was associated with slower motor skill acquisition.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Karen Nuytemans, Farid Rajabli, Melissa Jean-Francois, Jiji Thulaseedhara Kurup, Larry D. Adams, Takiyah D. Starks, Patrice L. Whitehead, Brian W. Kunkle, Allison Caban-Holt, Jonathan L. Haines, Michael L. Cuccaro, Jeffery M. Vance, Goldie S. Byrd, Gary W. Beecham, Christiane Reitz, Margaret A. Pericak-Vance
Summary: This study conducted genetic research on African American AD families and identified a significant linkage signal associated with AD, highlighting the importance of diverse population-level genetic data in understanding the genetic determinants of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Kazuya Suwabe, Ryuta Kuwamizu, Kazuki Hyodo, Toru Yoshikawa, Takeshi Otsuki, Asako Zempo-Miyaki, Michael A. Yassa, Hideaki Soya
Summary: Physical exercise has a positive impact on hippocampal memory decline with aging. Recent studies have shown that even light exercise can improve memory and this improvement is mediated by the ascending arousal system. This study aimed to investigate the effects of light-intensity exercise on hippocampal memory function in healthy older adults and found that pupil dilation during exercise played a role in the memory improvement.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Ajay Sood, Ana Werneck Capuano, Robert Smith Wilson, Lisa Laverne Barnes, Alifiya Kapasi, David Alan Bennett, Zoe Arvanitakis
Summary: The objective of this study was to explore the impact of metformin on cognition and brain pathology. The results showed that metformin users had slower decline in global cognition, episodic memory, and semantic memory compared to non-users. However, the relationship between metformin use and certain brain pathology remains uncertain.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Brian N. Lee, Junwen Wang, Molly A. Hall, Dokyoon Kim, Shana D. Stites, Li Shen
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. This study analyzed participants from the Alzheimer's Disease Neuroimaging Initiative and found differential associations between cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes, as well as variations between sexes. These findings suggest that sex differences may play a role in the development of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Thomas T. Austin, Christian L. Thomas, Ben Warren
Summary: This study investigated the effects of age on the robustness and resilience of auditory system using the desert locust. The researchers found that gene expression changes were mainly influenced by age rather than noise exposure. Both young and aged locusts were able to recover their auditory nerve function within 48 hours of noise exposure, but the recovery of transduction current magnitude was impaired in aged locusts. Key genes responsible for robustness to noise exposure in young locusts and potential candidates for compensatory mechanisms in auditory neurons of aged locusts were identified.
NEUROBIOLOGY OF AGING
(2024)
