Abstract
Abstract
Lafora disease (LD) is a fatal childhood-onset dementia characterized by the extensive accumulation of glycogen aggregates—the so-called Lafora Bodies (LBs)—in several organs. The accumulation of LBs in the brain underlies the neurological phenotype of the disease. LBs are composed of abnormal glycogen and various associated proteins, including p62, an autophagy adaptor that participates in the aggregation and clearance of misfolded proteins. To study the role of p62 in the formation of LBs and its participation in the pathology of LD, we generated a mouse model of the disease (malinKO) lacking p62. Deletion of p62 prevented LB accumulation in skeletal muscle and cardiac tissue. In the brain, the absence of p62 altered LB morphology and increased susceptibility to epilepsy. These results demonstrate that p62 participates in the formation of LBs and suggest that the sequestration of abnormal glycogen into LBs is a protective mechanism through which it reduces the deleterious consequences of its accumulation in the brain.
Funder
Ministerio de Ciencia, Innovación y Universidades
Instituto de Salud Carlos III
National Institute of Neurological Disorders and Stroke
Agencia Estatal de Investigación
Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya
Horizon 2020
Universitat Ramon Llull
Publisher
Springer Science and Business Media LLC
Subject
Neuroscience (miscellaneous),Cellular and Molecular Neuroscience,Neurology
Cited by
4 articles.
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