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)
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
Chemistry, Multidisciplinary
Fa-An Chao, Srisathiyanarayanan Dharmaiah, Troy Taylor, Simon Messing, William Gillette, Dominic Esposito, Dwight Nissley, Frank McCormick, R. Andrew Byrd, Dhirendra K. Simanshu, Gabriel Cornilescu
Summary: This article investigates the influence of conformational dynamics of RAS proteins on their interactions with downstream effectors and explains and predicts the altered binding affinities of different mutants.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(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.
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
Multidisciplinary Sciences
M. Frank Erasmus, Fortunato Ferrara, Sara D'Angelo, Laura Spector, Camila Leal-Lopes, Andre A. Teixeira, Jesper Sorensen, Suhani Nagpal, Kathryn Perea-Schmittle, Alok Choudhary, William Honnen, David Calianese, Luis Antonio Rodriguez Carnero, Simon Cocklin, Victor Greiff, Abraham Pinter, Andrew R. M. Bradbury
Summary: This study establishes NGS guidelines for therapeutic antibody discovery, demonstrating the advantages of NGS in expanding unique HCDR3 clusters, increasing high affinity antibodies, and improving lead prioritization. The study also reveals a lack of association between CDR frequencies derived from NGS and affinity.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Rebekah Tillotson, Justyna Cholewa-Waclaw, Kashyap Chhatbar, John C. Connelly, Sophie A. Kirschner, Shaun Webb, Martha V. Koerner, Jim Selfridge, David A. Kelly, Dina De Sousa, Kyla Brown, Matthew J. Lyst, Skirmantas Kriaucionis, Adrian Bird
Summary: The interaction of MeCP2 with sites of non-CG methylation, particularly mCAC, is crucial for normal brain function and may be related to the pathogenesis of Rett syndrome. Dysregulated genes in Mecp2 null and domain-swap mice are associated with other neurological disorders, suggesting potential targets for the Rett syndrome phenotype.
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
Biochemical Research Methods
Ayano Goto, Wataru Yoshida
Summary: A hybridization-based CpG methylation level detection method using methyl-CpG-binding domain-fused firefly luciferase (MBD-Fluc) was developed to quantify the CpG methylation levels of SEPT9, BRCA1, and LINE-1 oligonucleotides. It was demonstrated that methylated CpG of the target region could be accurately detected.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Qihang Wang, Song Luo, Danyang Xiong, Xiaole Xu, Xiaoyu Zhao, Lili Duan
Summary: DNA methylation is an important epigenetic marker that has gained attention due to three oxidative modifications (hmC, fC, and caC). Mutations in the MBD of MeCP2 result in Rett syndrome, but the effects of DNA modification and MBD mutations on interaction changes remain uncertain. Molecular dynamics simulations were used to investigate the underlying mechanisms, revealing that MBD has the strongest binding ability for mCDNA. The study emphasizes the necessity for targeted Rett compounds that enhance the stability and strength of MBD-DNA interactions.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Medicine, Research & Experimental
Joseph H. Lubin, Christopher Markosian, D. Balamurugan, Minh T. Ma, Chih-Hsiung Chen, Dongfang Liu, Renata Pasqualini, Wadih Arap, Stephen K. Burley, Sagar D. Khare
Summary: In this study, a structure-based pipeline was developed to analyze protein-protein interactions and immune evasion of SARS-CoV-2 variants. The results showed changes in interfacial interactions and weakened therapeutic antibody binding, providing insights into the molecular basis of immune evasion.
Article
Multidisciplinary Sciences
Abdulkhaleg Ibrahim, Christophe Papin, Kareem Mohideen-Abdul, Stephanie Le Gras, Isabelle Stoll, Christian Bronner, Stefan Dimitrov, Bruno P. Klaholz, Ali Hamiche
Summary: Studies have shown that MeCP2 is a microsatellite DNA binding protein that specifically recognizes 5hmC-modified CA repeat sequences, maintaining nucleosome-free regions in the genome. Dysfunction of MeCP2 may play a role in Rett syndrome.
Article
Multidisciplinary Sciences
Wanqiu Li, Linlin Wang, Bradley M. Wierbowski, Mo Lu, Feitong Dong, Wenchen Liu, Sisi Li, Peiyi Wang, Adrian Salic, Xin Gong
Summary: Dispatched (Disp) RND transporter, activated by Furin-mediated proteolytic cleavage, mediates the release of the lipid-modified Hedgehog (Hh) ligands. Structures of human Disp1 (hDisp1) before and after cleavage, and in complex with lipid-modified Sonic hedgehog (Shh), provide insights into the mechanisms of hDisp1 activation and function.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Elizabeth R. Gallagher, Erika L. F. Holzbaur
Summary: In response to lysosomal damage, the selective autophagy adaptor SQSTM1/p62 is recruited to damaged lysosomes and is required for lysophagic flux. The PB1 domain of p62 mediates oligomerization and is specifically required for lysophagy. p62 forms condensates on damaged lysosomes and HSP27 regulates these condensates, facilitating autophagosome formation.