X-chromosome regulation and sex differences in brain anatomy

Neuroscience & Biobehavioral Reviews, Journal Year: 2020, Volume and Issue: 120, P. 28 - 47

Published: Nov. 7, 2020

Humans show reproducible sex-differences in cognition and psychopathology that may be contributed to by influences of gonadal sex-steroids and/or sex-chromosomes on regional brain development. Gonadal are well known play a major role sexual differentiation the vertebrate brain, but far less is regarding sex-chromosomes. Our review focuses this latter issue bridging together two literatures have date been largely disconnected. We first consider "bottom-up" genetic molecular studies focused sex-chromosome gene content regulation. This literature nominates specific genes could drive developmental virtue their sex-biased expression functions within brain. then complementary "top down" view, from magnetic resonance imaging map sex- sex chromosome effects anatomy, link these maps gene-expression By connecting top-down bottom-up approaches, we emphasize potential X-linked driving development outline key goals for future work field.

Language: Английский

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DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1540 - 1540

Published: June 18, 2021

Cell cycle is regulated through numerous signaling pathways that determine whether cells will proliferate, remain quiescent, arrest, or undergo apoptosis. Abnormal cell regulation has been linked to many diseases. Thus, there an urgent need understand the diverse molecular mechanisms of how controlled. RNA helicases constitute a large family proteins with functions in all aspects metabolism, including unwinding annealing molecules regulate pre-mRNA, rRNA and miRNA processing, clamping protein complexes on RNA, remodeling ribonucleoprotein complexes, gene expression. also activity specific direct interaction. expression associated different diseases, cancer, neurological disorders, aging, autosomal dominant polycystic kidney disease (ADPKD) via range cellular processes such as proliferation, Recent studies showed participate progression at each phase, G1-S transition, S G2-M mitosis, cytokinesis. In this review, we discuss essential roles phases. For that, provide rich source targets for development therapeutic prophylactic drugs. We targeting strategies against helicases, types compounds explored, proposed inhibitory potential these treatment various disorders.

Language: Английский

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Prospective and detailed behavioral phenotyping in DDX3X syndrome

Molecular Autism, Journal Year: 2021, Volume and Issue: 12(1)

Published: May 16, 2021

Abstract Background DDX3X syndrome is a recently identified genetic disorder that accounts for 1–3% of cases unexplained developmental delay and/or intellectual disability (ID) in females, and associated with motor language delays, autism spectrum (ASD). To date, the published phenotypic characterization this has primarily relied on medical record review; addition, behavioral dimensions have not been fully explored. Methods We carried out multi-day, prospective, detailed phenotyping 14 females 1 male, focusing behavioral, psychological, neurological measures. Three participants cohort were previously reported limited phenotype information re-evaluated study. compared results against population norms contrasted phenotypes between individuals harboring either (1) protein-truncating variants or (2) missense in-frame deletions. Results Eighty percent (80%) met criteria ID, 60% ASD 53% attention-deficit/hyperactivity (ADHD). Motor delays common as sensory processing abnormalities. The included 5 missense, 3 intronic/splice-site, 2 nonsense, frameshift, deletions, one initiation codon variant. Genotype–phenotype correlations indicated that, average, variants/in-frame deletions more severe language, motor, adaptive deficits comparison to variants. Limitations Sample size modest, however, rare underdiagnosed disorder. Conclusion This study, representing first, syndrome, extends our understanding neurobehavioral phenotype. Gold-standard diagnostic approaches demonstrated high rates ASD, ADHD. In observed be key part syndrome. Even modest sample, we observe evidence genotype–phenotype generally phenotypes.

Language: Английский

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How mechanisms of stem cell polarity shape the human cerebral cortex

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(12), P. 711 - 724

Published: Sept. 30, 2022

Language: Английский

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The human DEAD-box helicase DDX3X as a regulator of mRNA translation

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 25, 2022

The human DEAD-box protein DDX3X is an RNA remodelling enzyme that has been implicated in various aspects of metabolism. In addition, like many proteins, it non-conventional functions are independent its enzymatic activity, e.g., acts as adaptor molecule innate immune signalling pathways. linked to several diseases. For example, somatic mutations were identified cancers, and de novo germline cause a neurodevelopmental condition now termed ‘DDX3X syndrome’. also important host factor different viral infections, where can have pro-or anti-viral effects depending on the specific virus. regulation translation initiation for mRNA transcripts likely central cellular function DDX3X, yet questions regarding exact targets mechanisms action remain unanswered. this review, we explore current knowledge about DDX3X’s physiological summarise interactions with machinery. A role translational reprogramming during stress emerging, may be involved granule formation mediating non-canonical initiation. Finally, discuss DDX3X-mediated infections. Dysregulation contributes involvement disease pathophysiology. Thus, better understanding regulating important, so potentially develop therapeutic strategies overcoming negative dysregulation.

Language: Английский

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