mGluR7 allosteric modulator AMN082 corrects protein synthesis and pathological phenotypes in FXS
This study uncovers novel functions of mGluR7 and AMN082 and suggests the activation of mGluR7 as a potential therapeutic approach for treating FXS.PMID:38374465 | DOI:10.1038/s44321-024-00038-w (Source: Molecular Medicine)
Source: Molecular Medicine - February 20, 2024 Category: Molecular Biology Authors: Vipendra Kumar Kwan Young Lee Anirudh Acharya Matthew S Babik Catherine A Christian-Hinman Justin S Rhodes Nien-Pei Tsai Source Type: research
Evaluating the clinical utility of a long-read sequencing-based approach in genetic testing of fragile-X syndrome
CONCLUSIONS: CAFXS represents a more comprehensive and accurate approach for FXS genetic testing that potentially enables more informed genetic counseling compared to PCR-based methods.PMID:38375623 | DOI:10.1016/j.cca.2023.117614 (Source: International Journal of Clinical Chemistry)
Source: International Journal of Clinical Chemistry - February 20, 2024 Category: Chemistry Authors: Fei Hou Aiping Mao Shan Shan Yan Li Wanli Meng Jiahan Zhan Wenying Nie Hua Jin Source Type: research
BREACHing new grounds in fragile X syndrome: Trinucleotide expansion linked to genome-wide heterochromatin domains and genome misfolding
In a recent study in Cell, Malachowski et al.1 show that the trinucleotide expansion in the FMR1 gene underlying fragile X syndrome triggers formation of large heterochromatin domains across the genome, resulting in the repression of synaptic genes housed within these domains. (Source: Molecular Cell)
Source: Molecular Cell - February 1, 2024 Category: Cytology Authors: Edda G. Schulz Tags: Spotlight Source Type: research
SRC family kinase inhibition rescues molecular and behavioral phenotypes, but not protein interaction network dynamics, in a mouse model of Fragile X syndrome
Molecular Psychiatry, Published online: 31 January 2024; doi:10.1038/s41380-024-02418-7SRC family kinase inhibition rescues molecular and behavioral phenotypes, but not protein interaction network dynamics, in a mouse model of Fragile X syndrome (Source: Molecular Psychiatry)
Source: Molecular Psychiatry - January 31, 2024 Category: Psychiatry Authors: Vera Stamenkovic Jonathan D. Lautz Felicia M. Harsh Stephen E. P. Smith Source Type: research
Similar Gap-Overlap Profiles in Children with Fragile X Syndrome and IQ-Matched Autism
CONCLUSION: Taken together, findings suggest that the social attention differences documented in FXS and ASD may be due to other cognitive factors, such as reward or motivation, rather than oculomotor control of visual attention.PMID:38246961 | DOI:10.1007/s10803-024-06245-1 (Source: Journal of Autism and Developmental Disorders)
Source: Journal of Autism and Developmental Disorders - January 21, 2024 Category: Psychiatry Authors: Carla A Wall Frederick Shic Elizabeth A Will Quan Wang Jane E Roberts Source Type: research
Autism Observation Scale for Infants: Systematic Review and Meta-Analysis in Samples at Increased Likelihood of Autism Spectrum Disorders
AbstractThe Autism Observation Scale for Infants (AOSI) is being applied to non infant sibling populations. Assessment of the tool ’s utility across increased likelihood (IL) populations is therefore needed. A systematic review and meta-analysis was conducted on 17 studies identified from six databases. The AOSI has been used in four IL contexts: infant siblings, infants with Fragile X Syndrome, Tuberous Sclerosis Complex, an d Down Syndrome. There were three main findings: (1) five studies report classification data though no consistent approach was used; (2) group differences between IL-ASD, IL non-ASD, and controls st...
Source: Review Journal of Autism and Developmental Disorders - January 18, 2024 Category: Child Development Source Type: research
Cannabinoid treatment for the symptoms of autism spectrum disorder
Expert Opin Emerg Drugs. 2024 Jan 16:1-15. doi: 10.1080/14728214.2024.2306290. Online ahead of print.ABSTRACTINTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 3% of school-age children. The core symptoms are deficits in social communication and restricted and repetitive patterns of behavior. Associated problems in cognition, language, behavior, sleep and mood are prevalent. Currently, no established pharmacological treatment exists for core ASD symptoms. Risperidone and aripiprazole are used to manage associated irritability, but their effectiveness is limited and adverse...
Source: Expert Opinion on Emerging Drugs - January 16, 2024 Category: Drugs & Pharmacology Authors: Adi Aran Dalit Cayam Rand Source Type: research
FMRP regulation of aggrecan mRNA translation controls perineuronal net development
Fragile X Messenger Ribonucleoprotein (FMRP) regulates translational efficiency of aggrecan mRNA through the protection of its poly(A) tail. Loss of FMRP leads to a reduction of aggrecan mRNA poly(A) tail length, which decreases the number of ribosomes that bind the mRNA to initiate translation. The reduction in Aggrecan protein levels results in a delay in formation of perineuronal nets (PNNs). PNNs are necessary for the excitatory/inhibitory (E/I) balance in the brain, which is disrupted in mouse models of Fragile X Syndrome (FXS), a neurodevelopmental disorder caused by the loss of FMRP. AbstractPerineuronal nets (PNNs)...
Source: Journal of Neurochemistry - January 16, 2024 Category: Neuroscience Authors: Heleen M. van't Spijker,
Joel D. Richter Tags: ORIGINAL ARTICLE Source Type: research
Cannabidiol (Epidyolex ®) for severe behavioral manifestations in patients with tuberous sclerosis complex, mucopolysaccharidosis type III and fragile X syndrome: protocol for a series of randomized, placebo-controlled N-of-1 trials
Many rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism spectrum disord... (Source: BMC Psychiatry)
Source: BMC Psychiatry - January 4, 2024 Category: Psychiatry Authors: A. R. M üller, B. den Hollander, P. M. van de Ven, K. C. B. Roes, L. Geertjens, H. Bruining, C. D. M. van Karnebeek, F. E. Jansen, M. C. Y. de Wit, L. W. ten Hoopen, A. B. Rietman, B. Dierckx, F. A. Wijburg, E. Boot, M. M. G. Brands and A. M. van Eeghen Tags: Study Protocol Source Type: research
Defects in AMPAR trafficking and microglia activation underlie socio-cognitive deficits associated to decreased expression of phosphodiesterase 2 a
Neurobiol Dis. 2023 Dec 26:106393. doi: 10.1016/j.nbd.2023.106393. Online ahead of print.ABSTRACTPhosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS. While the pharmacol...
Source: Neurobiology of Disease - December 28, 2023 Category: Neurology Authors: S ébastien Delhaye Marielle Jarjat Asma Boulksibat Clara Sanchez Alessandra Tempio Andrei Turtoi Mauro Giorgi Sandra Lacas-Gervais Gabriele Baj Carole Rovere Viviana Trezza Manuela Pellegrini Thomas Maurin Enzo Lalli Barbara Bardoni Source Type: research
Defects in AMPAR trafficking and microglia activation underlie socio-cognitive deficits associated to decreased expression of phosphodiesterase 2 a
Neurobiol Dis. 2023 Dec 26:106393. doi: 10.1016/j.nbd.2023.106393. Online ahead of print.ABSTRACTPhosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS. While the pharmacol...
Source: Neurobiology of Disease - December 28, 2023 Category: Neurology Authors: S ébastien Delhaye Marielle Jarjat Asma Boulksibat Clara Sanchez Alessandra Tempio Andrei Turtoi Mauro Giorgi Sandra Lacas-Gervais Gabriele Baj Carole Rovere Viviana Trezza Manuela Pellegrini Thomas Maurin Enzo Lalli Barbara Bardoni Source Type: research
Defects in AMPAR trafficking and microglia activation underlie socio-cognitive deficits associated to decreased expression of phosphodiesterase 2 a
Neurobiol Dis. 2023 Dec 26:106393. doi: 10.1016/j.nbd.2023.106393. Online ahead of print.ABSTRACTPhosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS. While the pharmacol...
Source: Neurobiology of Disease - December 28, 2023 Category: Neurology Authors: S ébastien Delhaye Marielle Jarjat Asma Boulksibat Clara Sanchez Alessandra Tempio Andrei Turtoi Mauro Giorgi Sandra Lacas-Gervais Gabriele Baj Carole Rovere Viviana Trezza Manuela Pellegrini Thomas Maurin Enzo Lalli Barbara Bardoni Source Type: research
Defects in AMPAR trafficking and microglia activation underlie socio-cognitive deficits associated to decreased expression of phosphodiesterase 2 a
Neurobiol Dis. 2023 Dec 26:106393. doi: 10.1016/j.nbd.2023.106393. Online ahead of print.ABSTRACTPhosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS. While the pharmacol...
Source: Neurobiology of Disease - December 28, 2023 Category: Neurology Authors: S ébastien Delhaye Marielle Jarjat Asma Boulksibat Clara Sanchez Alessandra Tempio Andrei Turtoi Mauro Giorgi Sandra Lacas-Gervais Gabriele Baj Carole Rovere Viviana Trezza Manuela Pellegrini Thomas Maurin Enzo Lalli Barbara Bardoni Source Type: research
Defects in AMPAR trafficking and microglia activation underlie socio-cognitive deficits associated to decreased expression of phosphodiesterase 2 a
Neurobiol Dis. 2023 Dec 26:106393. doi: 10.1016/j.nbd.2023.106393. Online ahead of print.ABSTRACTPhosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS. While the pharmacol...
Source: Neurobiology of Disease - December 28, 2023 Category: Neurology Authors: S ébastien Delhaye Marielle Jarjat Asma Boulksibat Clara Sanchez Alessandra Tempio Andrei Turtoi Mauro Giorgi Sandra Lacas-Gervais Gabriele Baj Carole Rovere Viviana Trezza Manuela Pellegrini Thomas Maurin Enzo Lalli Barbara Bardoni Source Type: research
Clinical and molecular characteristics of FMR1 microdeletion in patient with fragile X syndrome and review of the literature
CONCLUSION: According to review of previous cases with FMR1 microdeletions, most patients carrying concurrent deletion and full mutation had typical clinical features of FXS. To our knowledge, our case is the first to describe mosaicism of a premutation and microdeletion in the FMR1 gene. The patient was probably protected from the effects of the deletion by mosaicism with premutation allele, leading to milder phenotype. It is thus important to consider appropriate techniques for detecting FMR1 variants other than repeat expansions which cannot be detected by routine FXS diagnosis.PMID:38142803 | DOI:10.1016/j.cca.2023.117...
Source: International Journal of Clinical Chemistry - December 24, 2023 Category: Chemistry Authors: Areerat Hnoonual Oradawan Plong-On Juthamas Worachotekamjorn Chariyawan Charalsawadi Pornprot Limprasert Source Type: research
