Review
Psychiatry
Wei-Jia Zhang, Ling-Ling Shi, Li Zhang
Summary: This review article summarizes the research progress on cortical synaptic plasticity regulated by MeCP2 and the mechanisms underlying motor deficits caused by MeCP2 mutations. The potential of physical exercise and neuromodulation approaches in restoring neural plasticity and motor function is also evaluated. These findings contribute to the diagnosis and treatment of Rett syndrome.
WORLD JOURNAL OF PSYCHIATRY
(2022)
Article
Clinical Neurology
Xinyan Zhang, Marcel Smits, Leopold Curfs, Karen Spruyt
Summary: The study aims to characterize the sleep phenotypes of individuals with Rett Syndrome. The results show differences in sleep latency, total sleep time, and wake time after sleep onset among patients with different levels of clinical severity, particularly in hand functioning and walking. These differences are associated with increased deep sleep and reduced rapid eye movement sleep, which may be linked to (psycho)motor impairment in patients with MECP2 mutations.
Review
Genetics & Heredity
Katrina V. Good, John B. Vincent, Juan Ausio
Summary: Mutations in MeCP2 gene are the main cause of Rett syndrome, a neurodevelopmental disorder characterized by a period of normal development followed by regression. MeCP2 protein has multiple functions, including binding to methylated genomic DNA and playing a significant role in neuronal development. The variability in MeCP2 stability and its relationships with mRNA splicing, miRNA processing, and other non-coding RNAs may contribute to the epigenetic consequences of MeCP2 genetic ablation.
FRONTIERS IN GENETICS
(2021)
Article
Immunology
Huiping Li, Meixin Hu, Zhuxi Huang, Yi Wang, Ying Xu, Jingxin Deng, Ming Zhu, Weijun Feng, Xiu Xu
Summary: Mecp2-deficient mice show increased numbers of B cells and CD8(+) T cells in the meninges, as well as enhanced immune-related processes. This study reveals the significant role of meningeal immunity in Rett syndrome.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Keit Men Wong, Eike Wegener, Alireza Baradaran-Heravi, Brenda Huppke, Jutta Gaertner, Peter Huppke
Summary: Rett syndrome (RTT), caused by mutations in the MECP2 gene, is a severe neurodevelopmental disorder. Nonsense suppression therapy is a potential strategy for RTT patients with nonsense mutations. In this study, we evaluated the effect of CDX compounds on gentamicin-induced readthrough efficiency in MECP2 nonsense mutations. We found that CDX compounds potentiated readthrough and increased full-length MeCP2 protein levels. CDX5-288 showed the highest potency and allowed the use of reduced gentamicin doses. This combinatorial approach successfully upregulated Mecp2 protein expression in fibroblasts from Mecp2(R255X/Y) mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Baoyu Shen, Ruilin Zhang, Genmeng Yang, Yanxia Peng, Qianyun Nie, Hao Yu, Wenjuan Dong, Bingzheng Chen, Chunhui Song, Yan Tian, Lixiang Qin, Junjie Shu, Shijun Hong, Lihua Li
Summary: In the past decade, there has been a significant increase in methamphetamine (METH) abuse in the United States, East Asia, and Southeast Asia. METH abuse leads to drug dependence and irreversible neurotoxicity. Cannabidiol (CBD), a non-psychoactive cannabinoid from the cannabis plant, has shown neuroprotective, antioxidative, and anti-inflammatory properties under METH exposure. However, the underlying mechanisms of these properties are still unclear, hindering further research on CBD's therapeutic potential. This study found that CBD and METH may directly bind to the dopamine receptor D1 (DRD1) and CBD may compete with METH for binding sites. CBD pretreatment prevented METH-induced neurotoxicity by modulating DRD1-mediated phosphorylation of MeCP2 and Ca2+ signaling. These findings suggest that CBD could be a potential treatment for METH use disorders.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Eric Frankel, Avijit Podder, Megan Sharifi, Roshan Pillai, Newell Belnap, Keri Ramsey, Julius Dodson, Pooja Venugopal, Molly Brzezinski, Lorida Llaci, Brittany Gerald, Gabrielle Mills, Meredith Sanchez-Castillo, Chris D. Balak, Szabolcs Szelinger, Wayne M. Jepsen, Ashley L. Siniard, Ryan Richholt, Marcus Naymik, Isabelle Schrauwen, David W. Craig, Ignazio S. Piras, Matthew J. Huentelman, Nicholas J. Schork, Vinodh Narayanan, Sampathkumar Rangasamy
Summary: Through studying RTT-L patients, we discovered that their gene mutations are unrelated to RTT but cause a similar clinical phenotype. We analyzed the protein-protein interaction network of these genes and found that HDAC1 and CHD4 play important regulatory roles between RTT and RTT-L genes.
Article
Biochemistry & Molecular Biology
David Ortega-Alarcon, Rafael Claveria-Gimeno, Sonia Vega, Olga C. Jorge-Torres, Manel Esteller, Olga Abian, Adrian Velazquez-Campoy
Summary: Hydroxymethylated cytosine (5hmC) is a stable DNA epigenetic mark that interacts with MeCP2 in a distinct mode with a specific thermodynamic signature. Mutations associated with Rett syndrome alter the interaction between MeCP2 and dsDNA in a cytosine modification-specific manner, which may be correlated with disease onset time and clinical severity score.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Neurosciences
Gloria Brunori, Oliver B. Pelletier, Anna M. Stauffer, Janet D. Robishaw
Summary: The study reveals the importance of Gaolfb2c7/cAMP signaling in specific populations of MSNs in regulating motor behaviors, acting through D1R and A2AR to coordinate behavior. Additionally, the loss of Gaolfb2c7 in A2AR/D2R-MSNs leads to a hyperlocomotor phenotype and enhanced locomotor response to amphetamine.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Neurosciences
Ramona Cordani, Eleonora Tobaldini, Gabriel Dias Rodrigues, Donatella Giambersio, Marco Veneruso, Lorenzo Chiarella, Nicola Disma, Elisa De Grandis, Edgar Toschi-Dias, Ludovico Furlan, Angelica Carandina, Giulia Prato, Lino Nobili, Nicola Montano
Summary: Rett syndrome is a rare and severe neurological disorder mainly affecting females, usually caused by mutations in the MECP2 gene. It is characterized by loss of purposeful hand skills, gait abnormalities, loss of spoken language, stereotypic hand movements, epilepsy, and autonomic dysfunction. Understanding the neural mechanisms of autonomic dysfunction and its correlation with sudden death is essential for patient care.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Neurosciences
Stephen Shovlin, Chloe Delepine, Lindsay Swanson, Snow Bach, Mustafa Sahin, Mriganka Sur, Walter E. Kaufmann, Daniela Tropea
Summary: Rett syndrome is a neurodevelopmental disorder without effective treatments. Administration of Insulin-like Growth Factor 1 (IGF-1) and related compounds has shown promise in preclinical models but inconsistent results in clinical trials. A recent trial showed significant improvements in breathing phenotypes with IGF-1 treatment. RNA sequencing analysis identified differential gene expression associated with breathing phenotype improvement and suggested the involvement of inflammatory/immune pathways and IGF-1 signaling in treatment response.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Yuichi Akaba, Tadashi Shiohama, Yuji Komaki, Fumiko Seki, Alpen Ortug, Daisuke Sawada, Wataru Uchida, Koji Kamagata, Keigo Shimoji, Shigeki Aoki, Satoru Takahashi, Takeshi Suzuki, Jun Natsume, Emi Takahashi, Keita Tsujimura
Summary: Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in the MeCP2 gene. In this study, we used magnetic resonance imaging to investigate the neuroanatomy of the Mecp2-KO mouse brain. We found significant reductions in both global and local brain volumes, as well as changes in hemispheric asymmetry. These findings suggest that MeCP2 plays a role in the overall brain volume and region-specific brain structure.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Yuanlei Yue, Pan Xu, Zhichao Liu, Xiaoqian Sun, Juntao Su, Hongfei Du, Lingling Chen, Ryan T. Ash, Stelios Smirnakis, Rahul Simha, Linda Kusner, Chen Zeng, Hui Lu
Summary: Despite circuit hypoactivity and weakened functional connectivity across L2/3 and L5a, the firing pattern of the Mecp2-null circuit evolved with improved performance over the course of training. Trained mice not only showed improvements in motor learning, but also exhibited reduced anxiety and lived longer.
Article
Biochemistry & Molecular Biology
Yanling Li, Jiawei Qin, Menglu Chen, Nan Sun, Fangmei Tan, Hua Zhang, Yongdong Zou, Vladimir N. Uversky, Yun Liu
Summary: This paper investigates the structure and function of soybean GmMBD10c protein. Through bioinformatic prediction, circular dichroism, and nuclear magnetic resonance spectral analysis, it is found that part of the GmMBD10c protein is disordered. Experimental evidence shows that GmMBD10c protein can protect lactate dehydrogenase and other proteins from misfolding and aggregation induced by freeze-thaw process and heat stress. Moreover, overexpression of GmMBD10c enhances the salt tolerance of Escherichia coli. Overall, this research reveals the multifunctionality of GmMBD10c protein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jingwen Li, Patrick A. Kells, Ayla C. Osgood, Shree Hari Gautam, Woodrow L. Shew
Summary: The complex dynamics and coordination among neurons in the motor cortex are important for complex body movements. Excessive inhibition can lead to excessive synchrony among movement-related neurons, resulting in a collapse of complexity in the motor system and simpler behavior. This imbalance of inhibition may underlie abnormal motor function in conditions like Rett syndrome.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Cian-Ling Jhang, Tzyy-Nan Huang, Yi-Ping Hsueh, Wenlin Liao
HUMAN MOLECULAR GENETICS
(2017)
Article
Physiology
Kun-Ze Lee, Wenlin Liao
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2018)
Article
Anatomy & Morphology
Fang-Chi Kao, San-Hua Su, Gregory C. Carlson, Wenlin Liao
BRAIN STRUCTURE & FUNCTION
(2015)
Article
Neurosciences
Wenlin Liao, Michael J. Gandal, Richard S. Ehrlichman, Steven J. Siegel, Greg C. Carlson
NEUROBIOLOGY OF DISEASE
(2012)
Article
Multidisciplinary Sciences
Wen-Lin Liao, Hsiu-Chao Tsai, Hsiao-Fang Wang, Josephine Chang, Kuan-Ming Lu, Hsiao-Lin Wu, Yi-Chao Lee, Ting-Fen Tsai, Hiroshi Takahashi, Michael Wagner, Norbert B. Ghyselinck, Pierre Chambon, Fu-Chin Liu
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2008)
Article
Developmental Biology
Wenlin Liao
DEVELOPMENTAL NEUROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Cian-Ling Jhang, Hom-Yi Lee, Jin-Chung Chen, Wenlin Liao
HUMAN MOLECULAR GENETICS
(2020)
Article
Biochemistry & Molecular Biology
Wenlin Liao, Kun-Ze Lee
Summary: Cyclin-dependent kinase-like 5 (CDKL5) is an important regulator in neuronal development and function. Patients with CDKL5 deficiency disorder (CDD) often present with early-onset epilepsy. However, mouse models of CDD have not shown spontaneous seizures. In this study, the researchers found that mice lacking CDKL5 exhibited spontaneous epileptic EEG discharges at postnatal day 12, but these spikes disappeared after postnatal day 14. Transcriptome profiling revealed age-dependent and brain region-specific alterations of gene expression. These findings provide new insights into the etiology of CDD and potential targets for the treatment of neonatal epilepsy.
HUMAN MOLECULAR GENETICS
(2023)
Article
Anatomy & Morphology
WL Liao, HC Tsai, CY Wu, FC Liu
DEVELOPMENTAL DYNAMICS
(2005)
Article
Neurosciences
WL Liao, FC Liu
EUROPEAN JOURNAL OF NEUROSCIENCE
(2005)
Article
Anatomy & Morphology
WL Liao, HF Wang, HC Tsai, P Chambon, M Wagner, AK Kakizuka, FC Liu
DEVELOPMENTAL DYNAMICS
(2005)
Article
Neurosciences
YC Lee, CL Chien, CN Sun, CL Huang, NK Huang, MC Chiang, HL Lai, YS Lin, SY Chou, CKL Wang, MH Tai, WL Liao, TN Lin, FC Liu, Y Chern
EUROPEAN JOURNAL OF NEUROSCIENCE
(2003)