RESUMEN
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with a complex etiology. Recent evidence suggests that dopamine plays a crucial role in neural development. However, whether and how disrupted dopaminergic signaling during development contributes to ASD remains unknown. In this study, human brain RNA sequencing transcriptome analysis revealed a significant correlation between changes in dopaminergic signaling pathways and neural developmental signaling in ASD patients. In the zebrafish model, disrupted developmental dopaminergic signaling led to neural circuit abnormalities and behavior reminiscent of autism. Dopaminergic signaling may impact neuronal specification by potentially modulating integrins. These findings shed light on the mechanisms underlying the link between disrupted developmental dopamine signaling and ASD, and they point to the possibility of targeting dopaminergic signaling in early development for ASD treatment.
Asunto(s)
Trastorno del Espectro Autista , Dopamina , Fenotipo , Transducción de Señal , Pez Cebra , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/patología , Animales , Humanos , Dopamina/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Modelos Animales de Enfermedad , Masculino , Vías Nerviosas/metabolismo , Femenino , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patologíaRESUMEN
RNA-binding proteins (RBPs) bind to RNAs and are crucial for regulating RNA splicing, stability, translation, and transport. Among these proteins, the CUGBP Elav-like family (CELF) is a highly conserved group crucial for posttranscriptional regulation by binding to CUG repeats. Comprising CELF1-6, this family exhibits diverse expression patterns and functions. Dysregulation of CELF has been implicated in various neural disorders, encompassing both neurodegenerative and neurodevelopmental conditions, such as Alzheimer's disease and autism. This article aims to provide a comprehensive summary of the CELF family's role in neurodevelopment and neurodevelopmental disorders. Understanding CELF's mechanisms may offer clues for potential therapeutic strategies by regulating their targets in neurodevelopmental disorders.
Asunto(s)
Proteínas CELF , Trastornos del Neurodesarrollo , Humanos , Trastornos del Neurodesarrollo/genética , Animales , Proteínas CELF/metabolismo , Proteínas CELF/genéticaRESUMEN
A facile approach to develop the stable and well-defined bulk heterojunction (BHJ) nanomorphology has been demonstrated. Novel pyrene (Py)-functionalized diblock copolymers poly(3-hexylthiophene)-block-poly[3-(10-(pyren-1-yloxy)decyloxy)thiophene] (P3HT-b-P3TPy), and pyrene-functionalized fullerene [6,6]-phenyl-C61-butyric acid 1-pyrene butyl ester (PCBPy), were successfully synthesized. The π-π interactions of Py mesogens interdigitated between the functionalized fullerene and P3TPy segment can allow for the cooperative assembly of P3HT-b-P3TPy and PCBPy. The orientation of the Py mesogens also can further enhance the molecular arrangement. Compared with the as-cast and thermal annealing, solvent annealing can promote cooperative assembly of P3HT-b-P3TPy:PCBPy undergoing the slow film growth. Note that the assembly microstructure strongly depends on the molar ratio of P3HT and P3TPy with Py mesogens. Low loading of P3TPy block in the copolymers blends keeps the same behavior to the P3HT, whereas relatively high loading of Py mesogens favors the better intermolecular π-π stacking interactions between P3HT-b-P3TPy and PCBPy. As a result, the P3HT-b-P3TPy(3/1) forms the orientated nanowires with PCBPy in bulk heterojunction, and the average domain size is estimated to be 10-20 nm, which is desirable for enlarge surface area for donor/acceptor interfaces and give a bicontinuous pathway for efficient electron transfer. Furthermore, the cooperative assembly between P3HT-b-P3TPy and PCBPy is found to effectively suppress the PCBPy macrophase separation, and stabilize the blend morphology.