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Regolazione del calcio neuronale e stress cellulare nell’ipertermia maligna

Regolazione del calcio neuronale e stress cellulare nell’ipertermia maligna

Jason Santiago

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Editorial:
KS OmniScriptum Publishing
Año de edición:
2024
Materia
Ciencia: cuestiones generales
ISBN:
9786208140670
50,67 €
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Sobre IBD

Gli ioni calcio (Ca2+) sono molecole di segnalazione essenziali e devono essere attentamente regolati per preservare la specificità della funzione. Una proteina di segnalazione del Ca2+ indispensabile è il canale di rilascio del calcio del recettore della rianodina (RyR). RyR1 è essenziale per la contrazione muscolare e le mutazioni di RyR1 possono portare a gravi disturbi muscolari come l’ipertermia maligna (MH). Recentemente, è stato sviluppato un modello murino di MH umana (Y522S-RyR1). Nel muscolo scheletrico, Y522S-RyR1 mostra una maggiore sensibilità all’attivazione con conseguente perdita di Ca2+, disorganizzazione mitocondriale e stress cellulare. Sebbene l’espressione di RyR1 sia limitata nel cervello, il cervelletto potrebbe essere particolarmente vulnerabile a questa malattia perché RyR1 è altamente espresso nei neuroni Purkinje. In questo studio, Y522S-RyR1 nelle cellule di Purkinje presenta una soglia di attivazione più bassa, ma non causa gravi stress e danni cellulari. Le future indagini sui meccanismi di compensazione per l’aumento del rilascio di Ca2+ nelle cellule di Purkinje potrebbero avere un valore terapeutico per molti disturbi neurologici e muscolari.

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