Article
Biochemistry & Molecular Biology
Dragana D. Protic, Ramkumar Aishworiya, Maria Jimena Salcedo-Arellano, Si Jie Tang, Jelena Milisavljevic, Filip Mitrovic, Randi J. Hagerman, Dejan B. Budimirovic
Summary: FXS is a neurodevelopmental disorder that can be improved through early diagnosis and interventions targeting behavior symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Azalea Lee, Jie Xu, Zhexing Wen, Peng Jin
Summary: Fragile X syndrome is the most common inherited cause of intellectual disability and autism spectrum disorder. Human induced pluripotent stem cells provide a unique means of studying FXS pathophysiology specific to humans.
Article
Clinical Neurology
Michael J. Hurley, Robert M. J. Deacon, A. W. Edith Chan, David Baker, David L. Selwood, Patricia Cogram
Summary: Fragile X syndrome, the most common inherited intellectual disability and mono-genetic cause of autism spectrum disorder, is associated with CGG trinucleotide expansion in the FMR1 gene and reduced activity of large-conductance calcium-activated potassium channels. The use of the potassium channel activator VSN16R showed promising results in improving behavioral deficits in a mouse model of fragile X syndrome, suggesting its potential therapeutic value.
Article
Neurosciences
Juan Zhao, Jin Xue, Tengfei Zhu, Hua He, Huaixing Kang, Xuan Jiang, Wen Huang, Ranhui Duan
Summary: Fragile X syndrome (FXS) is a genetic disorder caused by the lack of functional fragile X mental retardation protein (FMRP), which leads to intellectual disability. Recent research identified collapsing response mediator protein (CRMP) as a target of FMRP, and targeting CRMP ameliorated circadian defects in FXS fruit flies.
NEUROSCIENCE BULLETIN
(2021)
Article
Medicine, Research & Experimental
Karima Habbas, Oktay Cakil, Boglarka Zambo, Ricardos Tabet, Fabrice Riet, Doulaye Dembele, Jean-Louis Mandel, Michael Hocquemiller, Ralph Laufer, Francoise Piguet, Herve Moine
Summary: Fragile X syndrome (FXS) is a common form of familial intellectual disability caused by the lack of RNA-binding protein FMRP. This study demonstrates that DGKk, an mRNA target of FMRP and a regulator of lipid signaling, plays an important role in FXS pathogenesis, and the delivery of modified and FMRP-independent DGKk can correct abnormal lipid signaling and behavioral phenotypes in FXS mice.
EMBO MOLECULAR MEDICINE
(2022)
Article
Clinical Neurology
Tarjani Shukla, June Bryan de la Pena, John M. Perish, Jonathan E. Ploski, Craig R. Stumpf, Kevin R. Webster, Catherine A. Thorn, Zachary T. Campbell
Summary: Fragile X syndrome is the most common inherited source of intellectual disability in humans, caused by epigenetic silencing of the Fmr1 gene. The MNK inhibitor eFT508 shows potential in alleviating deficits associated with FXS by targeting downstream pathways. This study highlights the ability of eFT508 to improve various phenotypic abnormalities linked to FXS.
Review
Neurosciences
Snow Bach, Stephen Shovlin, Michael Moriarty, Barbara Bardoni, Daniela Tropea
Summary: RTT and FXS are two monogenetic neurodevelopmental disorders with overlapping features possibly due to interactions between MeCP2 and FMRP. Both syndromes affect brain development and result in dysregulation of common molecular signaling pathways.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Pernille Bulow, Menahem Segal, Gary J. Bassell
Summary: This article discusses the emergence of hyperexcitability in neurodevelopmental disorders and explores recent advances in understanding novel mechanisms in Fragile X syndrome (FXS), providing new therapeutic strategies for FXS and other neurodevelopmental disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Magdalena Kalinowska, Mathijs B. van der Lei, Michael Kitiashvili, Maggie Mamcarz, Mauricio M. Oliveira, Francesco Longo, Eric Klann
Summary: This study found that de novo protein synthesis was elevated in hippocampal parvalbumin and somatostatin-expressing inhibitory neurons in Fmr1 knockout mice. Cell type-specific deletion of Fmr1 in parvalbumin-expressing neurons resulted in anxiety-like behavior, impaired social behavior, and dysregulated de novo protein synthesis. In contrast, deletion of Fmr1 in somatostatin-expressing neurons did not result in behavioral abnormalities and did not significantly impact de novo protein synthesis.
Review
Pharmacology & Pharmacy
Randi J. Hagerman, Paul J. Hagerman
Summary: Fragile X syndrome is a common form of inherited intellectual disability and autism spectrum disorder, caused by large expansions of noncoding CGG repeats in the FMR1 gene. While there is currently no direct way to reverse the loss of FMRP, there is potential for effective treatments targeting dysregulated pathways in the near future.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2022)
Article
Psychiatry
David C. Stoppel, Patrick K. McCamphill, Rebecca K. Senter, Arnold J. Heynen, Mark F. Bear
Summary: Fragile X syndrome is caused by silencing of the human FMR1 gene and is the leading monogenic cause of intellectual disability and autism. Studies indicate that long-term use of mGluR5 NAMs may lead to the development of treatment resistance, likely occurring at signaling nodes downstream.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Immunology
Peifeng Guo, Xinyu Yang, Xiaomeng Guo, Huaien Yang, Jiao Pan, Yue Li
Summary: Fragile X syndrome (FXS) is a common inherited intellectual disability caused by a lack of FMRP. Gastrointestinal problems in FXS are associated with gut microbial dysbiosis, inflammation, and increased intestinal permeability. Our findings demonstrate that omega-3 PUFAs improve autistic behaviors and gut homeostasis in FMRP-deficient mice by suppressing gut microbiota dysbiosis, offering a novel therapeutic approach for juvenile FXS treatment.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Review
Clinical Neurology
Ramkumar Aishworiya, Dragana Protic, Randi Hagerman
Summary: There is increasing recognition of the heterogeneity of origin of cases of autism spectrum disorder (ASD), with genetic etiology identified in 20-40% of cases. The Fragile X premutation state is a newly discovered disease state associated with various disorders, including ASD, and understanding molecular mechanisms may facilitate targeted treatments in the future.
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
B. Di Marco, P. Dell'Albani, S. D'Antoni, M. Spatuzza, C. M. Bonaccorso, S. A. Musumeci, F. Drago, B. Bardoni, M. V. Catania
Summary: The study found a novel modulatory role of mGlu5 receptor in SGs formation, providing new perspectives for understanding cellular response to stress in FXS pathophysiology.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Nutrition & Dietetics
Cara J. Westmark
Summary: The study found associations between the use of soy-based infant formula and worsened autistic behaviors in females and males with fragile X syndrome. It suggests the need for prospective evaluation of soy-based infant formula on disease comorbidities in fragile X syndrome, and supports further investigation into early gastrointestinal problems in the syndrome. The findings also indicate that premutation fragile X mothers should be encouraged to breastfeed, based on data from the Fragile X Syndrome Nutrition Study.
