Connexins and Pannexins: Important Players in Neurodevelopment, Neurological Diseases, and Potential Therapeutics

Daniela Baracaldo; María Gabriela Corrales Hernández; Maria Camila Ortiz-Vergara; Valeria Cormane Alfaro; Ricardo-Miguel Luque-Bernal; Carlos-Alberto Calderon-Ospina; Juan-Fernando Cediel-Becerra

doi:10.3390/biomedicines10092237

Connexins and Pannexins: Important Players in Neurodevelopment, Neurological Diseases, and Potential Therapeutics

Título traducido de la contribución: Conexinas y panexinas: actores importantes en el neurodesarrollo, enfermedades neurológicas y posibles terapias

Daniela Baracaldo, María Gabriela Corrales Hernández, Maria Camila Ortiz-Vergara, Valeria Cormane Alfaro, Ricardo-Miguel Luque-Bernal, Carlos-Alberto Calderon-Ospina, Juan-Fernando Cediel-Becerra

Producción científica: Contribución a una revista › Artículo de revisión › revisión exhaustiva

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Resumen

La comunicación entre células es esencial para el desarrollo embrionario adecuado y su disfunción puede provocar enfermedades. Investigaciones recientes han llamado la atención sobre un nuevo grupo de moléculas llamadas conexinas (Cxs) y panexinas (Panxs). Las Cx se han descrito durante más de cuarenta años como reguladores fundamentales de la embriogénesis; sin embargo, el mecanismo exacto por el cual proporcionan esta regulación no ha sido claramente dilucidado. En consecuencia, Cxs y Panxs se han relacionado con enfermedades neurodegenerativas congénitas como la enfermedad de Charcot-Marie-Tooth y, más recientemente, la apertura crónica de hemicanales se ha asociado con enfermedades neurodegenerativas en adultos (p. ej., enfermedad de Alzheimer). Se cree que la comunicación entre células a través de uniones hexaméricas formadas por conjuntos hexaméricos de Cx, conocidos como conexiones, es un componente crucial en la regulación del desarrollo. En cuanto a los Panx, a pesar de ser topológicamente similares a los Cx, parecen formar predominantemente canales que conectan el citoplasma con el espacio extracelular y, a pesar de investigaciones recientes sobre la expresión de Panx1 (Pannexin 1) en diferentes regiones del cerebro durante la fase embrionaria, se ha demostrado que estudiado en menor medida. Cuando se trata del sistema nervioso, Cxs y Panxs desempeñan un papel importante en las primeras etapas del desarrollo neuronal con un amplio rango de acción que va desde la migración celular durante las primeras etapas hasta la diferenciación neuronal y la formación de circuitos del sistema. En esta revisión, describimos la evidencia disponible más reciente sobre los aspectos moleculares y estructurales de los canales Cx y Panx, su papel en el neurodesarrollo, las enfermedades neurológicas congénitas y del adulto, y finalmente proponemos cómo la modulación farmacológica de estos canales podría modificar la patogénesis de algunas enfermedades. .

Título traducido de la contribución	Conexinas y panexinas: actores importantes en el neurodesarrollo, enfermedades neurológicas y posibles terapias
Idioma original	Inglés estadounidense
Número de artículo	2237
Publicación	Biomedicines
Volumen	10
N.º	9
DOI	https://doi.org/10.3390/biomedicines10092237
Estado	Publicada - sep. 9 2022

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title = "Connexins and Pannexins: Important Players in Neurodevelopment, Neurological Diseases, and Potential Therapeutics",

abstract = "Cell-to-cell communication is essential for proper embryonic development and its dysfunction may lead to disease. Recent research has drawn attention to a new group of molecules called connexins (Cxs) and pannexins (Panxs). Cxs have been described for more than forty years as pivotal regulators of embryogenesis; however, the exact mechanism by which they provide this regulation has not been clearly elucidated. Consequently, Cxs and Panxs have been linked to congenital neurodegenerative diseases such as Charcot-Marie-Tooth disease and, more recently, chronic hemichannel opening has been associated with adult neurodegenerative diseases (e.g., Alzheimer{\textquoteright}s disease). Cell-to-cell communication via gap junctions formed by hexameric assemblies of Cxs, known as connexons, is believed to be a crucial component in developmental regulation. As for Panxs, despite being topologically similar to Cxs, they predominantly seem to form channels connecting the cytoplasm to the extracellular space and, despite recent research into Panx1 (Pannexin 1) expression in different regions of the brain during the embryonic phase, it has been studied to a lesser degree. When it comes to the nervous system, Cxs and Panxs play an important role in early stages of neuronal development with a wide span of action ranging from cellular migration during early stages to neuronal differentiation and system circuitry formation. In this review, we describe the most recent available evidence regarding the molecular and structural aspects of Cx and Panx channels, their role in neurodevelopment, congenital and adult neurological diseases, and finally propose how pharmacological modulation of these channels could modify the pathogenesis of some diseases.",

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AU - Baracaldo, Daniela

AU - Hernández, María Gabriela Corrales

AU - Ortiz-Vergara, Maria Camila

AU - Alfaro, Valeria Cormane

AU - Luque-Bernal, Ricardo-Miguel

AU - Calderon-Ospina, Carlos-Alberto

AU - Cediel-Becerra, Juan-Fernando

PY - 2022/9/9

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AB - Cell-to-cell communication is essential for proper embryonic development and its dysfunction may lead to disease. Recent research has drawn attention to a new group of molecules called connexins (Cxs) and pannexins (Panxs). Cxs have been described for more than forty years as pivotal regulators of embryogenesis; however, the exact mechanism by which they provide this regulation has not been clearly elucidated. Consequently, Cxs and Panxs have been linked to congenital neurodegenerative diseases such as Charcot-Marie-Tooth disease and, more recently, chronic hemichannel opening has been associated with adult neurodegenerative diseases (e.g., Alzheimer’s disease). Cell-to-cell communication via gap junctions formed by hexameric assemblies of Cxs, known as connexons, is believed to be a crucial component in developmental regulation. As for Panxs, despite being topologically similar to Cxs, they predominantly seem to form channels connecting the cytoplasm to the extracellular space and, despite recent research into Panx1 (Pannexin 1) expression in different regions of the brain during the embryonic phase, it has been studied to a lesser degree. When it comes to the nervous system, Cxs and Panxs play an important role in early stages of neuronal development with a wide span of action ranging from cellular migration during early stages to neuronal differentiation and system circuitry formation. In this review, we describe the most recent available evidence regarding the molecular and structural aspects of Cx and Panx channels, their role in neurodevelopment, congenital and adult neurological diseases, and finally propose how pharmacological modulation of these channels could modify the pathogenesis of some diseases.

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Connexins and Pannexins: Important Players in Neurodevelopment, Neurological Diseases, and Potential Therapeutics

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