scholarly journals Rett syndrome from bench to bedside: recent advances

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 398 ◽  
Author(s):  
Yann Ehinger ◽  
Valerie Matagne ◽  
Laurent Villard ◽  
Jean-Christophe Roux
Keyword(s):  
Transcriptional Regulation ◽  
Rett Syndrome ◽  
Neurological Disorder ◽  
De Novo ◽  
Binding Protein ◽  
Chromatin Organization ◽  
Molecular Function ◽  
Therapeutic Approaches ◽  
Cellular Models ◽  
Recent Advances

Rett Syndrome is a severe neurological disorder mainly due to de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Mecp2 is known to play a role in chromatin organization and transcriptional regulation. In this review, we report the latest advances on the molecular function of Mecp2 and the new animal and cellular models developed to better study Rett syndrome. Finally, we present the latest innovative therapeutic approaches, ranging from classical pharmacology to correct symptoms to more innovative approaches intended to cure the pathology.

scholarly journals Towards a better diagnosis and treatment of Rett syndrome: a model synaptic disorder

Brain ◽  
2019 ◽  
Vol 142 (2) ◽  
pp. 239-248 ◽  
Author(s):  
Abhishek Banerjee ◽  
Meghan T Miller ◽  
Keji Li ◽  
Mriganka Sur ◽  
Walter E Kaufmann
Keyword(s):  
Clinical Trials ◽  
Rett Syndrome ◽  
Therapeutic Interventions ◽  
Diagnosis And Treatment ◽  
Therapeutic Approaches ◽  
Preclinical Models ◽  
Lessons Learnt ◽  
Recent Advances

Fifty years after the first publication on Rett syndrome, Banerjee et al. review the molecular, cellular and circuit neurobiology of the disorder. They summarize recent advances in therapeutic interventions explored in preclinical models, as well as lessons learnt from past clinical trials and how these might inform future therapeutic approaches.

scholarly journals Ten novel insertion/deletion variants in MECP2 identified in Japanese patients with Rett syndrome

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Eri Takeshita ◽  
Aritoshi Iida ◽  
Chihiro Abe-Hatano ◽  
Eiji Nakagawa ◽  
Masayuki Sasaki ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Neurological Disorder ◽  
Binding Protein ◽  
Japanese Patients ◽  
Gene Encoding ◽  
Pathogenic Variants

Abstract Rett syndrome (RTT) is an X-linked progressive and severe neurological disorder caused by mutations in the gene encoding methyl CpG binding protein 2 (MECP2). Among the 49 typical RTT patients examined, we identified 10 novel and eight known insertion/deletion variants, and 31 known pathogenic variants in MECP2. The pathogenic variants presented here should be a useful resource for examining the correlation between the genotypes and phenotypes of RTT.

scholarly journals MeCP2 and Chromatin Compartmentalization

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 878 ◽  
Author(s):  
Annika Schmidt ◽  
Hui Zhang ◽  
M. Cristina Cardoso
Keyword(s):  
Transcriptional Regulation ◽  
Rett Syndrome ◽  
Chromatin Structure ◽  
Binding Protein ◽  
Higher Order ◽  
Functional Domains ◽  
Genome Architecture

Methyl-CpG binding protein 2 (MeCP2) is a multifunctional epigenetic reader playing a role in transcriptional regulation and chromatin structure, which was linked to Rett syndrome in humans. Here, we focus on its isoforms and functional domains, interactions, modifications and mutations found in Rett patients. Finally, we address how these properties regulate and mediate the ability of MeCP2 to orchestrate chromatin compartmentalization and higher order genome architecture.

scholarly journals A Novel Methyl-CpG Binding Protein 2 (MECP2) Variant in an Indian Girl with Rett Syndrome

2021 ◽  
Author(s):  
Pratiksha Chheda ◽  
Shailesh Pande ◽  
Tavisha Dama ◽  
Dollar Goradia ◽  
Sushant Vinarkar
Keyword(s):  
Rett Syndrome ◽  
De Novo ◽  
Binding Protein ◽  
Neurodevelopmental Disorder ◽  
Missense Variant ◽  
Clinical Findings ◽  
Indian Girl ◽  
Gene Coding ◽  
Gradual Loss ◽  
Repetitive Movements

Rett syndrome is an X-linked dominant disorder that is primarily seen in females and is linked to mutations in the gene coding for Methyl-CpG Binding Protein 2 (MECP2). It is a neurodevelopmental disorder characterised by impairments in language, repetitive movements, early-onset seizures, delayed growth, autistic features, intellectual disability and abnormal Electroencephalograms (EEG). Author’s reported a case of three year six months old Indian girl who was born of a nonconsanguineous marriage presented with stereotypic hand movements, gradual loss of speech, inability to walk independently and frequent episodes of seizure. Genetic testing for analysis of MECP2 mutations was performed and a novel de novo missense variant (c.361G>A, p.Asp121Asn) was identified, which was predicted to be disease causing on the basis of insilico analysis and clinical findings. The study suggested that a careful evaluation of the pathogenic nature of MECP2 variants supports clinical diagnosis and aids in genetic counseling and patient management.

Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with bone disease severity in Rett syndrome

2019 ◽  
Author(s):  
Carla Caffarelli ◽  
Tomai Pitinca Maria Dea ◽  
Valentina Francolini ◽  
Roberto Canitano ◽  
felice Claudio De ◽  
...  
Keyword(s):  
Disease Severity ◽  
Rett Syndrome ◽  
Bone Disease ◽  
Binding Protein ◽  
Mecp2 Mutation ◽  
Mutation Type

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

scholarly journals Carrot Supplementation Improves Blood Pressure and Reduces Aortic Root Lesions in an Atherosclerosis-Prone Genetic Mouse Model

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1181
Author(s):  
Raffaella Soleti ◽  
Marine Coué ◽  
Charlotte Trenteseaux ◽  
Gregory Hilairet ◽  
Lionel Fizanne ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mouse Model ◽  
Aortic Root ◽  
De Novo ◽  
Body Weight Gain ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Hemodynamic Parameters ◽  
Cellular Models ◽  
Genetic Mouse Model

Epidemiological studies have shown that carrot consumption may be associated with a lower risk of developing several metabolic dysfunctions. Our group previously determined that the Bolero (Bo) carrot variety exhibited vascular and hepatic tropism using cellular models of cardiometabolic diseases. The present study evaluated the potential metabolic and cardiovascular protective effect of Bo, grown under two conditions (standard and biotic stress conditions (BoBS)), in apolipoprotein E-knockout (ApoE−/−) mice fed with high fat diet (HFD). Effects on metabolic/hemodynamic parameters and on atherosclerotic lesions have been assessed. Both Bo and BoBS decreased plasma triglyceride and expression levels of genes implicated in hepatic de novo lipogenesis and lipid oxidation. BoBS supplementation decreased body weight gain, secretion of very-low-density lipoprotein, and increased cecal propionate content. Interestingly, Bo and BoBS supplementation improved hemodynamic parameters by decreasing systolic, diastolic, and mean blood pressure. Moreover, Bo improved cardiac output. Finally, Bo and BoBS substantially reduced the aortic root lesion area. These results showed that Bo and BoBS enriched diets corrected most of the metabolic and cardiovascular disorders in an atherosclerosis-prone genetic mouse model and may therefore represent an interesting nutritional approach for the prevention of cardiovascular diseases.

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