Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease

Ariadna Laguna, Nicoletta Schintu, André Nobre, Alexandra Alvarsson, Nikolaos Volakakis, Jesper Kjaer Jacobsen, Marta Gómez-Galán, Elena Sopova, Eliza Joodmardi, Takashi Yoshitake, Qiaolin Deng, Jan Kehr, Johan Ericson, Per Svenningsson, Oleg Shupliakov, Thomas Perlmann

Research output

41 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)826-835
Number of pages10
JournalNature Neuroscience
Volume18
Issue number6
DOIs
Publication statusPublished - 28 Jun 2015

Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease'. Together they form a unique fingerprint.

  • Cite this

    Laguna, A., Schintu, N., Nobre, A., Alvarsson, A., Volakakis, N., Jacobsen, J. K., Gómez-Galán, M., Sopova, E., Joodmardi, E., Yoshitake, T., Deng, Q., Kehr, J., Ericson, J., Svenningsson, P., Shupliakov, O., & Perlmann, T. (2015). Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease. Nature Neuroscience, 18(6), 826-835. https://doi.org/10.1038/nn.4004