Targeted Treatments for Fragile X Syndrome
Adv Neurobiol. 2023;30:225-253. doi: 10.1007/978-3-031-21054-9_10.ABSTRACTThe histories of targeted treatment trials in fragile X syndrome (FXS) are reviewed in animal studies and human trials. Advances in understanding the neurobiology of FXS have identified a number of pathways that are dysregulated in the absence of FMRP and are therefore pathways that can be targeted with new medication. The utilization of quantitative outcome measures to assess efficacy in multiple studies has improved the quality of more recent trials. Current treatment trials including the use of cannabidiol (CBD) topically and metformin orally have...
Source: Adv Data - March 17, 2023 Category: Epidemiology Authors: Devon Johnson Courtney Clark Randi Hagerman Source Type: research
Fragile X mental retardation protein coordinates neuron-to-glia communication for clearance of developmentally transient brain neurons
Proc Natl Acad Sci U S A. 2023 Mar 21;120(12):e2216887120. doi: 10.1073/pnas.2216887120. Epub 2023 Mar 15.ABSTRACTIn the developmental remodeling of brain circuits, neurons are removed by glial phagocytosis to optimize adult behavior. Fragile X mental retardation protein (FMRP) regulates neuron-to-glia signaling to drive glial phagocytosis for targeted neuron pruning. We find that FMRP acts in a mothers against decapentaplegic (Mad)-insulin receptor (InR)-protein kinase B (Akt) pathway to regulate pretaporter (Prtp) and amyloid precursor protein-like (APPL) signals directing this glial clearance. Neuronal RNAi of Drosophil...
Source: Appl Human Sci - March 15, 2023 Category: Physiology Authors: Chunzhu Song Kendal Broadie Source Type: research
Fragile X mental retardation protein coordinates neuron-to-glia communication for clearance of developmentally transient brain neurons
Proc Natl Acad Sci U S A. 2023 Mar 21;120(12):e2216887120. doi: 10.1073/pnas.2216887120. Epub 2023 Mar 15.ABSTRACTIn the developmental remodeling of brain circuits, neurons are removed by glial phagocytosis to optimize adult behavior. Fragile X mental retardation protein (FMRP) regulates neuron-to-glia signaling to drive glial phagocytosis for targeted neuron pruning. We find that FMRP acts in a mothers against decapentaplegic (Mad)-insulin receptor (InR)-protein kinase B (Akt) pathway to regulate pretaporter (Prtp) and amyloid precursor protein-like (APPL) signals directing this glial clearance. Neuronal RNAi of Drosophil...
Source: Appl Human Sci - March 15, 2023 Category: Physiology Authors: Chunzhu Song Kendal Broadie Source Type: research
Fragile X mental retardation protein coordinates neuron-to-glia communication for clearance of developmentally transient brain neurons
Proc Natl Acad Sci U S A. 2023 Mar 21;120(12):e2216887120. doi: 10.1073/pnas.2216887120. Epub 2023 Mar 15.ABSTRACTIn the developmental remodeling of brain circuits, neurons are removed by glial phagocytosis to optimize adult behavior. Fragile X mental retardation protein (FMRP) regulates neuron-to-glia signaling to drive glial phagocytosis for targeted neuron pruning. We find that FMRP acts in a mothers against decapentaplegic (Mad)-insulin receptor (InR)-protein kinase B (Akt) pathway to regulate pretaporter (Prtp) and amyloid precursor protein-like (APPL) signals directing this glial clearance. Neuronal RNAi of Drosophil...
Source: Appl Human Sci - March 15, 2023 Category: Physiology Authors: Chunzhu Song Kendal Broadie Source Type: research
Fragile X mental retardation protein coordinates neuron-to-glia communication for clearance of developmentally transient brain neurons
Proc Natl Acad Sci U S A. 2023 Mar 21;120(12):e2216887120. doi: 10.1073/pnas.2216887120. Epub 2023 Mar 15.ABSTRACTIn the developmental remodeling of brain circuits, neurons are removed by glial phagocytosis to optimize adult behavior. Fragile X mental retardation protein (FMRP) regulates neuron-to-glia signaling to drive glial phagocytosis for targeted neuron pruning. We find that FMRP acts in a mothers against decapentaplegic (Mad)-insulin receptor (InR)-protein kinase B (Akt) pathway to regulate pretaporter (Prtp) and amyloid precursor protein-like (APPL) signals directing this glial clearance. Neuronal RNAi of Drosophil...
Source: Appl Human Sci - March 15, 2023 Category: Physiology Authors: Chunzhu Song Kendal Broadie Source Type: research
Fragile X mental retardation protein coordinates neuron-to-glia communication for clearance of developmentally transient brain neurons
Proc Natl Acad Sci U S A. 2023 Mar 21;120(12):e2216887120. doi: 10.1073/pnas.2216887120. Epub 2023 Mar 15.ABSTRACTIn the developmental remodeling of brain circuits, neurons are removed by glial phagocytosis to optimize adult behavior. Fragile X mental retardation protein (FMRP) regulates neuron-to-glia signaling to drive glial phagocytosis for targeted neuron pruning. We find that FMRP acts in a mothers against decapentaplegic (Mad)-insulin receptor (InR)-protein kinase B (Akt) pathway to regulate pretaporter (Prtp) and amyloid precursor protein-like (APPL) signals directing this glial clearance. Neuronal RNAi of Drosophil...
Source: Appl Human Sci - March 15, 2023 Category: Physiology Authors: Chunzhu Song Kendal Broadie Source Type: research
Fragile X mental retardation protein coordinates neuron-to-glia communication for clearance of developmentally transient brain neurons
Proc Natl Acad Sci U S A. 2023 Mar 21;120(12):e2216887120. doi: 10.1073/pnas.2216887120. Epub 2023 Mar 15.ABSTRACTIn the developmental remodeling of brain circuits, neurons are removed by glial phagocytosis to optimize adult behavior. Fragile X mental retardation protein (FMRP) regulates neuron-to-glia signaling to drive glial phagocytosis for targeted neuron pruning. We find that FMRP acts in a mothers against decapentaplegic (Mad)-insulin receptor (InR)-protein kinase B (Akt) pathway to regulate pretaporter (Prtp) and amyloid precursor protein-like (APPL) signals directing this glial clearance. Neuronal RNAi of Drosophil...
Source: Appl Human Sci - March 15, 2023 Category: Physiology Authors: Chunzhu Song Kendal Broadie Source Type: research
The nuclear isoforms of the Fragile X Mental Retardation RNA-binding Protein associate with genomic DNA bridges
In this study, we discovered that nuclear FMRP isoforms specifically associate with DNA bridges, aberrant genomic structures that form during mitosis and whose accumulation can drive genome instability by inducing DNA damage. Further localisation studies showed that a subset of FMRP-positive bridges contain proteins that have been shown to associate with specific DNA bridges known as ultrafine DNA bridges (UFBs), and surprisingly are RNA positive. Significantly, the depletion of nuclear FMRP isoforms promotes the accumulation of DNA bridges, correlating with the accumulation of DNA damages and cell death, unveiling an impo...
Source: Mol Biol Cell - March 8, 2023 Category: Molecular Biology Authors: N Ledoux W Gauthier-Naud O Lavoie V Watters S Hussein P Adjibade R Mazroui Source Type: research
Efficacy of cannabinoids in neurodevelopmental and neuropsychiatric disorders among children and adolescents: a systematic review
AbstractA better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of cannabinoid-based products (CBP). We provide a systematic review of the rationale and current clinical trial evidence for CBP in the treatment of neuropsychiatric and neurodevelopmental disorders in children and adolescents. A systematic search of MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Trials was performed to identify articles published after 1980 about CBP for medical purposes in individuals aged 18 years or younger with selected...
Source: European Child and Adolescent Psychiatry - March 3, 2023 Category: Psychiatry Source Type: research
Dietary fish oil improves autistic behaviors and gut homeostasis by altering the gut microbial composition in a mouse model of fragile X syndrome
Brain Behav Immun. 2023 Feb 27:S0889-1591(23)00050-8. doi: 10.1016/j.bbi.2023.02.019. Online ahead of print.ABSTRACTFragile X syndrome (FXS) is the most common inherited intellectual disability, caused by a lack of the fragile X mental retardation protein (FMRP). Individuals with neurodevelopmental disorders frequently experience gastrointestinal problems that are primarily linked to gut microbial dysbiosis, inflammation, and increased intestinal permeability. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are non-pharmacological agents that exert potential therapeutic effects against neurological disorders. However, ...
Source: Brain, Behavior, and Immunity - March 1, 2023 Category: Neurology Authors: Peifeng Guo Xinyu Yang Xiaomeng Guo Huaien Yang Jiao Pan Yue Li Source Type: research
Axonal and presynaptic FMRP: Localization, signal, and functional implications
Hear Res. 2023 Feb 11;430:108720. doi: 10.1016/j.heares.2023.108720. Online ahead of print.ABSTRACTFragile X mental retardation protein (FMRP) binds a selected set of mRNAs and proteins to guide neural circuit assembly and regulate synaptic plasticity. Loss of FMRP is responsible for Fragile X syndrome, a neuropsychiatric disorder characterized with auditory processing problems and social difficulty. FMRP actions in synaptic formation, maturation, and plasticity are site-specific among the four compartments of a synapse: presynaptic and postsynaptic neurons, astrocytes, and extracellular matrix. This review summarizes adva...
Source: Hearing Research - February 22, 2023 Category: Audiology Authors: Xiaoyu Wang Dalit Sela-Donenfeld Yuan Wang Source Type: research
Axonal and presynaptic FMRP: Localization, signal, and functional implications
Hear Res. 2023 Feb 11;430:108720. doi: 10.1016/j.heares.2023.108720. Online ahead of print.ABSTRACTFragile X mental retardation protein (FMRP) binds a selected set of mRNAs and proteins to guide neural circuit assembly and regulate synaptic plasticity. Loss of FMRP is responsible for Fragile X syndrome, a neuropsychiatric disorder characterized with auditory processing problems and social difficulty. FMRP actions in synaptic formation, maturation, and plasticity are site-specific among the four compartments of a synapse: presynaptic and postsynaptic neurons, astrocytes, and extracellular matrix. This review summarizes adva...
Source: Hearing Research - February 22, 2023 Category: Audiology Authors: Xiaoyu Wang Dalit Sela-Donenfeld Yuan Wang Source Type: research
Altered GnRH neuron and ovarian innervation characterize reproductive dysfunction linked to the Fragile X messenger ribonucleoprotein (Fmr1) gene mutation
ConclusionThese results reveal Fmr1 function in the regulation of GnRH neuron secretion, and point to the role of GnRH neurons, in addition to the ovarian innervation, in the etiology of Fmr1-mediated reproductive disorders. (Source: Frontiers in Endocrinology)
Source: Frontiers in Endocrinology - February 22, 2023 Category: Endocrinology Source Type: research
Molecules, Vol. 28, Pages 1889: mTOR Signaling Disruption and Its Association with the Development of Autism Spectrum Disorder
m Sadek
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication along with repetitive stereotypic behaviors. Currently, there are no specific biomarkers for diagnostic screening or treatments available for autistic patients. Numerous genetic disorders are associated with high prevalence of ASD, including tuberous sclerosis complex, phosphatase and tensin homolog, and fragile X syndrome. Preclinical investigations in animal models of these diseases have revealed irregularities in the PI3K/Akt/mTOR signaling pathway as well as ASD-relate...
Source: Molecules - February 16, 2023 Category: Chemistry Authors: Shilu Deepa Thomas Niraj Kumar Jha Shreesh Ojha Bassem Sadek Tags: Review Source Type: research
Genes, Vol. 14, Pages 505: Efficient Delivery of FMR1 across the Blood Brain Barrier Using AAVphp Construct in Adult FMR1 KO Mice Suggests the Feasibility of Gene Therapy for Fragile X Syndrome
Conclusion: These experiments demonstrate efficient, brain-specific delivery of Fmr1 via peripheral administration in adult mice. The gene delivery led to partial alleviation of the Fmr1 KO phenotypical behaviors. FMRP oversupply may explain why not all behaviors were significantly affected. Since AAV.php vectors are less efficient in humans than in the mice used in the current experiment, studies to determine the optimal dose using human-suitable vectors will be necessary to further demonstrate feasibility. (Source: Genes)
Source: Genes - February 16, 2023 Category: Genetics & Stem Cells Authors: Kathryn K. Chadman Tatyana Adayev Aishwarya Udayan Rida Ahmed Chun-Ling Dai Jeffrey H. Goodman Harry Meeker Natalia Dolzhanskaya Milen Velinov Tags: Article Source Type: research
