Pyruvate dehydrogenase kinase 2 knockdown restores the ability of amyotrophic lateral sclerosis-linked SOD1G93A rat astrocytes to support motor neuron survival by increasing mitochondrial respiration
作者：
Ernesto Miquel;Rosalía Villarino;Laura Martínez-Palma;Adriana Cassina;Patricia Cassina*
通讯作者：
Patricia Cassina
作者机构：
Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
Departamento de Bioquímica, Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
通讯机构：
Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
语种：
英文
关键词：
ALS,astrocytes,mitochondria,PDK2
期刊：
Glia
ISSN：
0894-1491
年：
2024
卷：
72
期：
5
页码：
999-1011
会议名称：
16th European Meeting on Glial Cells in Health and Disease
会议时间：
JUL 08-11, 2023
会议地点：
Berlin, GERMANY
基金类别：
Programa de Desarrollo de las Ciencias Basicas(PEDECIBA); Agencia Nacional deInvestigacion e Innovacion [FCE_1_2019_1_156461
摘要：
Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron (MN) degeneration. Various studies using cellular and animal models of ALS indicate that there is a complex interplay between MN and neighboring non-neuronal cells, such as astrocytes, resulting in noncell autonomous neurodegeneration. Astrocytes in ALS exhibit a lower ability to support MN survival than nondisease-associated ones, which is strongly correlated with low-mitochondrial respiratory activity. Indeed, pharmacological inhibition of pyruvate dehydrogenase kinase (PDK) led to an increase in the mitochondrial oxidative phosphorylation pathway as the primary source of cell energy in SOD...
