Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy.
Cell Death Dis
; 9(11): 1100, 2018 10 27.
Article
en En
| MEDLINE
| ID: mdl-30368521
ABSTRACT
Spinal Muscular Atrophy (SMA) is caused by genetic mutations in the SMN1 gene, resulting in drastically reduced levels of Survival of Motor Neuron (SMN) protein. Although SMN is ubiquitously expressed, spinal motor neurons are one of the most affected cell types. Previous studies have identified pathways uniquely activated in SMA motor neurons, including a hyperactivated ER stress pathway, neuronal hyperexcitability, and defective spliceosomes. To investigate why motor neurons are more affected than other neural types, we developed a spinal organoid model of SMA. We demonstrate overt motor neuron degeneration in SMA spinal organoids, and this degeneration can be prevented using a small molecule inhibitor of CDK4/6, indicating that spinal organoids are an ideal platform for therapeutic discovery.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Piperazinas
/
Piridinas
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Organoides
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Inhibidores de Proteínas Quinasas
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Quinasa 4 Dependiente de la Ciclina
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Quinasa 6 Dependiente de la Ciclina
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Bibliotecas de Moléculas Pequeñas
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Neuronas Motoras
Idioma:
En
Revista:
Cell Death Dis
Año:
2018
Tipo del documento:
Article
País de afiliación:
Singapur