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Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease.
Laguna, Ariadna; Schintu, Nicoletta; Nobre, André; Alvarsson, Alexandra; Volakakis, Nikolaos; Jacobsen, Jesper Kjaer; Gómez-Galán, Marta; Sopova, Elena; Joodmardi, Eliza; Yoshitake, Takashi; Deng, Qiaolin; Kehr, Jan; Ericson, Johan; Svenningsson, Per; Shupliakov, Oleg; Perlmann, Thomas.
Afiliación
  • Laguna A; 1] Ludwig Institute for Cancer Research, Stockholm, Sweden. [2] Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. [3] Neurodegenerative Diseases Group, Vall d'Hebron Research Institute-CIBERNED, Barcelona, Spain.
  • Schintu N; Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Nobre A; Ludwig Institute for Cancer Research, Stockholm, Sweden.
  • Alvarsson A; Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Volakakis N; Ludwig Institute for Cancer Research, Stockholm, Sweden.
  • Jacobsen JK; Ludwig Institute for Cancer Research, Stockholm, Sweden.
  • Gómez-Galán M; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Sopova E; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Joodmardi E; Ludwig Institute for Cancer Research, Stockholm, Sweden.
  • Yoshitake T; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
  • Deng Q; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
  • Kehr J; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
  • Ericson J; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
  • Svenningsson P; Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Shupliakov O; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Perlmann T; 1] Ludwig Institute for Cancer Research, Stockholm, Sweden. [2] Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Nat Neurosci ; 18(6): 826-35, 2015 Jun.
Article en En | MEDLINE | ID: mdl-25915474
The role of developmental transcription factors in maintenance of neuronal properties and in disease remains poorly understood. Lmx1a and Lmx1b are key transcription factors required for the early specification of ventral midbrain dopamine (mDA) neurons. Here we show that conditional ablation of Lmx1a and Lmx1b after mDA neuron specification resulted in abnormalities that show striking resemblance to early cellular abnormalities seen in Parkinson's disease. We found that Lmx1b was required for the normal execution of the autophagic-lysosomal pathway and for the integrity of dopaminergic nerve terminals and long-term mDA neuronal survival. Notably, human LMX1B expression was decreased in mDA neurons in brain tissue affected by Parkinson's disease. Thus, these results reveal a sustained and essential requirement of Lmx1b for the function of midbrain mDA neurons and suggest that its dysfunction is associated with Parkinson's disease pathogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Autofagia / Factores de Transcripción / Dopamina / Proteínas con Homeodominio LIM / Lisosomas Límite: Animals / Humans Idioma: En Revista: Nat Neurosci Asunto de la revista: NEUROLOGIA Año: 2015 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Autofagia / Factores de Transcripción / Dopamina / Proteínas con Homeodominio LIM / Lisosomas Límite: Animals / Humans Idioma: En Revista: Nat Neurosci Asunto de la revista: NEUROLOGIA Año: 2015 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos