Article
Pharmacology & Pharmacy
Mohamed Z. Habib, Esraa M. Elnahas, Yasmin M. Aboul-Ela, Mai A. Ebeid, Marwa Tarek, Doaa R. Sadek, Eman A. Negm, Dina A. Abdelhakam, Sawsan Aboul-Fotouh
Summary: Several reports suggest that calcium permeable AMPA glutamate receptors with RNA hypo-editing at the GluA2 Q/R site and excitotoxicity-mediated neuronal death play a role in the pathogenesis of neurological disorders including autism spectrum disorder (ASD). This study examined the effects of risperidone treatment on Adar2 expression, GluA2 editing, oxidative/nitrosative stress, and neuronal death in a rat model of ASD. The results showed that risperidone improved behavioral deficits and increased Adar2 expression and GluA2 editing, while reducing oxidative/nitrosative stress and neurodegeneration.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Loredana Frassinelli, Elisa Orecchini, Sofian Al-Wardat, Marco Tripodi, Carmine Mancone, Margherita Doria, Silvia Galardi, Silvia Anna Ciafre, Alessandro Michienzi
Summary: ADAR2 acts as a suppressor of L1 retrotransposition by inhibiting its activity, forming a complex with multiple non-ribosomal ADAR2-interacting factors.
Article
Hematology
Mingrui Guo, Tim Hon Man Chan, Qiling Zhou, Omer An, Ying Li, Yangyang Song, Zi Hui Tan, Vanessa Hui En Ng, Philomina Sona Peramangalam, Zhi Qing Tan, Xinang Cao, Eisaku Iwanaga, Masao Matsuoka, Melissa G. M. Ooi, Wei Ying Jen, Liang Piu Koh, Esther Chan, Lip Kun Tan, Yufen Goh, Wilson Wang, Bryan T. H. Koh, Chan Ming Chun, Melissa J. Fullwood, Wee Joo Chng, Motomi Osato, John Anto Pulikkan, Henry Yang, Leilei Chen, Daniel G. Tenen
Summary: Adenosine deaminases acting on RNA (ADAR) family of enzymes, especially ADAR2, play a role in multiple cancers. This study shows that ADAR2 is downregulated in certain types of acute myeloid leukemia (AML) and suppresses leukemogenesis in AML cells with t(8;21) or inv(16) translocations, through its RNA editing function.
Article
Biochemistry & Molecular Biology
Casey S. Jacobsen, Prince Salvador, John F. Yung, Sabrina Kragness, Herra G. Mendoza, Gail Mandel, Peter A. Beal
Summary: Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosine to inosine in duplex RNA, resulting in an effective A-to-G edit. ADAR editing can lead to recoding events and alterations in RNA function. One limitation of ADAR is its preference for editing adenosines with specific neighboring nucleotides, but new strategies and approaches are being developed to overcome this.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biology
Dhruva Katrekar, Yichen Xiang, Nathan Palmer, Anushka Saha, Dario Meluzzi, Prashant Mali
Summary: Adenosine deaminases acting on RNA (ADARs) have potential for programmable RNA editing, but their exogenous delivery leads to non-specific targeting and low enzymatic activity on certain RNA motifs. By performing a deep mutational scan of the ADAR2 deaminase domain, we improved enzymatic activity and developed a split-ADAR2 deaminase with significantly higher specificity for RNA editing. This systematic engineering of the ADAR2 deaminase domain has important implications for RNA biotechnology applications.
Article
Biochemistry & Molecular Biology
America Chandia-Cristi, Nicolas Stuardo, Cristian Trejos, Nancy Leal, Daniela Urrutia, Francisca C. Bronfman, Alejandra Alvarez Rojas
Summary: Brain-derived neurotrophic factor (BDNF) activates TrkB receptor and downstream pathways, promoting neuronal survival, growth, and plasticity. The role of c-Abl, a non-receptor tyrosine kinase, in BDNF-induced dendritic arborization was examined using various strategies. Surprisingly, BDNF promoted c-Abl activation and interaction with TrkB receptors. Inhibition or genetic ablation of c-Abl abolished BDNF-induced dendritic arborization without affecting classic TrkB downstream pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Oncology
Ananya Hariharan, Weihong Qi, Hubert Rehrauer, Licun Wu, Manuel Ronner, Martin Wipplinger, Jelena Kresoja-Rakic, Suna Sun, Lucia Oton-Gonzalez, Marika Sculco, Veronique Serre-Beinier, Clement Meiller, Christophe Blanquart, Jean-Francois Fonteneau, Bart Vrugt, Jan Hendrik Ruschoff, Isabelle Opitz, Didier Jean, Marc de Perrot, Emanuela Felley-Bosco
Summary: This study found increased levels of ADAR-mediated RNA editing in mesothelioma tumors and primary cultures compared to mesothelial cells. Heterogeneity in editing was observed between tumor samples and primary cultures. ADAR2 expression levels were higher in BRCA1-associated protein 1 wild-type tumors and correlated with changes in RNA editing in transcripts and 3'UTR. ADAR2 was found to play a role in cell proliferation, cell cycle, sensitivity to antifolate treatment, and type-1 interferon signaling, leading to changes in the microenvironment in vivo.
MOLECULAR ONCOLOGY
(2022)
Article
Neurosciences
Joel G. Hashimoto, Mo L. Singer, Calla M. Goeke, Fuming Zhang, Yuefan Song, Ke Xia, Robert J. Linhardt, Marina Guizzetti
Summary: This study investigated the effects of a neonatal handling protocol on dendritic arborization and glycosaminoglycan (GAG) levels in the developing brain. Sex differences were found in both dendritic arborization and HS-GAG levels, with an increase observed in females but not males. Additionally, neonatal handling led to changes in GAG levels in the hippocampus in both males and females, indicating a similar stress response in both sexes.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Neurosciences
David M. Steffen, Camille M. Hanes, Kar Men Mah, Paula Valino Ramos, Peter J. Bosch, Dalton C. Hinz, Jason J. Radley, Robert W. Burgess, Andrew M. Garrett, Joshua A. Weiner
Summary: The establishment of a functional cerebral cortex relies on the proper execution of various developmental steps, which includes dendritic and axonal outgrowth, synaptic connection formation and maturation. Dysregulation of these processes can result in improper neuronal connectivity, including neurodevelopmental disorders. The y-Protocadherins (y-Pcdhs) are involved in multiple aspects of neurodevelopment, including neuronal survival, dendrite arborization, and synapse development. The specific role of each individual y-Pcdh family member remains unclear.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Sergei G. Gaidin, Artem M. Kosenkov
Summary: This review summarizes the current data on the mechanism and role of pre-mRNA editing of KAR subunits in the mammalian brain and proposes future research perspectives.
REVIEWS IN THE NEUROSCIENCES
(2022)
Article
Developmental Biology
Najat Dzaki, Shufeng Bu, Samuel Song Yuan Lau, Wei Lin Yong, Fengwei Yu
Summary: A study found that the Drosophila GSK3β homologue, Sgg, is cell-autonomously required for dendrite pruning of sensory neurons. Sgg promotes microtubule depolymerization and reorganization to facilitate dendrite pruning.
Article
Geriatrics & Gerontology
Shou-Zen Fan, Chih-Wei Sung, Yi-Hsuan Tsai, Sheng-Rong Yeh, Wei-Sheng Lin, Pei-Yu Wang
Summary: The reduced expression of the Indy gene has been shown to extend lifespan in Caenorhabditis elegans and Drosophila melanogaster, as well as improve the metabolic health of Mus musculus by inducing a physiological status similar to dietary restriction. The deletion of the mammalian Indy gene (mIndy, SLC13A5) in mice significantly enhances memory performance and motor coordination, similar to what is observed in animals under dietary restriction. Tissue-specific deletion of mIndy in the nervous system is sufficient to improve memory performance, indicating a critical role for brain-derived mIndy expression in regulating memory function.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Article
Biochemical Research Methods
Helena Chaytow, Ilda Sethw Hassan, Sara Akbar, Linda Popplewell, George Dickson, Philip E. Chen
Summary: The GluA2 subunit of AMPA receptors undergoes RNA editing at a specific site mediated by ADAR2, which is critical for regulating calcium permeability. In this study, PMOs were used to increase editing efficiency by affecting the alternative splicing of ADAR2, leading to enhanced RNA editing of the GluA2 subunit. This method presents a validated approach for investigating downstream cellular processes related to altered ADAR2 activity.
JOURNAL OF NEUROSCIENCE METHODS
(2021)
Article
Neurosciences
Erkang Fei, Peng Chen, Qian Zhang, Yanzi Zhong, Tian Zhou
Summary: This study reveals that S10 phosphorylation of Dysbindin-1A by Akt1 is essential for neuronal development. Overexpression of wild type or S10 phospho-mimic mutant of Dysbindin-1A can rescue the dendrite and spine deficits in Dysbindin-1A knockdown neurons.