Synaptic cell adhesion molecules contribute to the pathogenesis and progression of fragile X syndrome.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a monogenic cause of autism spectrum disorders. Deficiencies in the fragile X messenger ribonucleoprotein, encoded by the FMR1 gene, lead to various anatomical and pathophysiological abnormalities and behavioral deficits, such as spine dysmorphogenesis and learning and memory impairments. Synaptic cell adhesion molecules (CAMs) play crucial roles in synapse formation and neural signal transmission by promoting the formation of new synaptic contacts, accurately organizing presynaptic and postsynaptic protein complexes, and ensuring the accuracy of signal transmission. Recent studies have implicated synaptic CAMs such as the immunoglobulin superfamily, N-cadherin, leucine-rich repeat proteins, and neuroligin-1 in the pathogenesis of FXS and found that they contribute to defects in dendritic spines and synaptic plasticity in FXS animal models. This review systematically summarizes the biological associations between nine representative synaptic CAMs and FMRP, as well as the functional consequences of the interaction, to provide new insights into the mechanisms of abnormal synaptic development in FXS.

The potential role of ribonucleic acid methylation in the pathological mechanisms of fragile X syndrome.

Fragile X syndrome (FXS) is a common inherited cause of intellectual disabilities and single-gene cause of autism spectrum disorder (ASD), resulting from the loss of functional fragile X messenger ribonucleoprotein (FMRP), an RNA-binding protein (RBP) encoded by the fragile X messenger ribonucleoprotein 1 (FMR1) gene. Ribonucleic acid (RNA) methylation can lead to developmental diseases, including FXS, through various mechanisms mediated by 5-hydroxymethylcytosine, 5-methylcytosine, N6-methyladenosine, etc. Emerging evidence suggests that modifications of some RNA species have been linked to FXS. However, the underlying pathological mechanism has yet to be elucidated. In this review, we reviewed the implication of RNA modification in FXS and summarized its specific characteristics for facilitating the identification of new therapeutic targets.

Cerebellum neuropathology and motor skill deficits in fragile X syndrome.

Fragile X syndrome (FXS) is a leading form of inherited intellectual disability and single-gene cause of autism spectrum disorder (ASD) and is characterized by core deficits in cognitive flexibility, sensory sensitivity, emotion, and social interactions. Motor deficits are a shared feature of FXS and autism. The cerebellum has emerged as one of the target brain areas affected by neurodevelopmental diseases. Alterations in the cerebellar structure, circuits, and function may be the key drivers of impaired fine and gross motor skills in FXS and fragile X-associated tremor/ataxia syndrome (FXTAS). In this review, we briefly examined recent findings in FXS and present a discussion on the literature supporting motor skill deficits in FXS. Subsequently, we focused on neuropathological alterations in the cerebellum in FXS and FXTAS. We highlight studies that have directly examined the function of fragile X mental retardation protein and related epigenetic variations in the cerebellum. Overall, we obtained considerable supporting evidence for the hypothesis that cerebellar dysfunction is evident in FXS and FXTAS; however, compared with studies on other ASD models, studies on motor skills related to fragile X disorders are particularly rare and inconclusive. Hence, future research should address FXS-related motor and behavioral trajectories and examine the underlying mechanisms at both the cell and circuit levels.

Dynamic regulation and key roles of ribonucleic acid methylation.

Ribonucleic acid (RNA) methylation is the most abundant modification in biological systems, accounting for 60% of all RNA modifications, and affects multiple aspects of RNA (including mRNAs, tRNAs, rRNAs, microRNAs, and long non-coding RNAs). Dysregulation of RNA methylation causes many developmental diseases through various mechanisms mediated by N 6-methyladenosine (m6A), 5-methylcytosine (m5C), N 1-methyladenosine (m1A), 5-hydroxymethylcytosine (hm5C), and pseudouridine (Ψ). The emerging tools of RNA methylation can be used as diagnostic, preventive, and therapeutic markers. Here, we review the accumulated discoveries to date regarding the biological function and dynamic regulation of RNA methylation/modification, as well as the most popularly used techniques applied for profiling RNA epitranscriptome, to provide new ideas for growth and development.

8-[(3-Phenyl-1,2,4-oxa-diazol-5-yl)meth-oxy]quinoline monohydrate.

In the title compound, C18H13N3O2·H2O, the oxa-diazole ring forms dihedral angles 7.21 (10) and 21.25 (11)° with the quinoline and benzene rings, respectively. The crystal structure features O-H⋯N hydrogen bonds and is further consolidated by C-H⋯O hydrogen-bonding inter-actions involving the water molecule of hydration.

8-{[3-(3-Meth-oxy-phen-yl)-1,2,4-oxa-diazol-5-yl]meth-oxy}quinoline monohydrate.

In the title hydrate, C19H15N3O3·H2O, the three aromatic groups in the quinoline derivative are close to coplanar: the central oxa-diazole fragment makes dihedral angles of 15.7 (2)° with the benzene ring and 5.30 (14)° with the quinoline ring system. In the crystal, the organic mol-ecules are connected with water mol-ecules by pairs of O-H⋯N hydrogen bonds involving the quinoline and oxa-diazole N atoms. The mol-ecules form stacks along the a axis, neighboring mol-ecules within each stack being related by inversion and the shortest distance between the centroids of the oxa-diazole and pyridine rings being 3.500 (2) Å. Mol-ecules from neighboring stacks are linked by weak C-H⋯O hydrogen bonds, forming a three-dimensional structure.

5-Nitro-1-benzofuran-2(3H)-one.

In the crystal structure of the title compound, C(8)H(5)NO(4), essentially planar mol-ecules [largest deviation from the least-squares plane = 0.030 (2) Å] form stacks along the a-axis direction. Intercentroid separations between overlapping benzene rings within the stack are 3.6594 (12) Šand 3.8131 (12) Å. Mol-ecules from neighboring stacks are linked by weak C-H⋯O hydrogen bonds into inversion dimers.