title: Malin knockout mice support a primary role of autophagy in the pathogenesis of Lafora disease.
abstract: Lafora disease (LD), a fatal neurodegenerative disorder characterized by intracellular inclusions called Lafora bodies (LBs), is caused by recessive loss-of-function mutations in the genes encoding either laforin or malin. Previous studies suggested a role of these proteins in regulating glycogen biosynthesis, in glycogen dephosphorylation and in the modulation of intracellular proteolytic systems. However, the contribution of each of these processes to LD pathogenesis is unclear. Here we review our recent finding that dysfunction of autophagy is a common feature of both laforin- and malin-deficient mice, preceding other pathological manifestations. We propose that autophagy plays a primary role in LD pathogenesis and is a potential target for its treatment.
authors.affiliation: Laboratory of Cellular Biology, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Erwin
authors.initials: E
authors.lastname: Knecht
authors.forename: Olga
authors.initials: O
authors.lastname: Criado-García
authors.forename: Carmen
authors.initials: C
authors.lastname: Aguado
authors.forename: Javier
authors.initials: J
authors.lastname: Gayarre
authors.forename: Lara
authors.initials: L
authors.lastname: Duran-Trio
authors.forename: Ana M
authors.initials: AM
authors.lastname: Garcia-Cabrero
authors.forename: Santiago
authors.initials: S
authors.lastname: Vernia
authors.forename: Beatriz
authors.initials: B
authors.lastname: San Millán
authors.forename: Miguel
authors.initials: M
authors.lastname: Heredia
authors.forename: Carlos
authors.initials: C
authors.lastname: Romá-Mateo
authors.forename: Silvana
authors.initials: S
authors.lastname: Mouron
authors.forename: Lucía
authors.initials: L
authors.lastname: Juana-López
authors.forename: Mercedes
authors.initials: M
authors.lastname: Domínguez
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Jose M
authors.initials: JM
authors.lastname: Serratosa
authors.forename: Marina
authors.initials: M
authors.lastname: Sanchez
authors.forename: Pascual
authors.initials: P
authors.lastname: Sanz
authors.forename: Paola
authors.initials: P
authors.lastname: Bovolenta
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodríguez de Córdoba
mesh_terms: D000818:Animals; D001343:Autophagy; D020192:Lafora Disease / Q000209:etiology* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency* / Q000378:metabolism
chemical_list: C572596:NHLRC1 protein, mouse; D044767:Ubiquitin-Protein Ligases