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

Результат исследований: Научные публикации в периодических изданияхстатья

35 Цитирования (Scopus)

Выдержка

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.

Язык оригиналаанглийский
Страницы (с-по)826-835
Число страниц10
ЖурналNature Neuroscience
Том18
Номер выпуска6
DOI
СостояниеОпубликовано - 28 июн 2015

Отпечаток

Mesencephalon
Parkinson Disease
Dopaminergic Neurons
Transcription Factors
Dopamine
Maintenance
Brain

Предметные области Scopus

  • Нейробиология (все)

Цитировать

Laguna, A., Schintu, N., Nobre, A., Alvarsson, A., Volakakis, N., Jacobsen, J. K., ... 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
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. / Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease. В: Nature Neuroscience. 2015 ; Том 18, № 6. стр. 826-835.
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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.",
author = "Ariadna Laguna and Nicoletta Schintu and Andr{\'e} Nobre and Alexandra Alvarsson and Nikolaos Volakakis and Jacobsen, {Jesper Kjaer} and Marta G{\'o}mez-Gal{\'a}n and Elena Sopova and Eliza Joodmardi and Takashi Yoshitake and Qiaolin Deng and Jan Kehr and Johan Ericson and Per Svenningsson and Oleg Shupliakov and Thomas Perlmann",
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Laguna, A, Schintu, N, Nobre, A, Alvarsson, A, Volakakis, N, Jacobsen, JK, 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, том. 18, № 6, стр. 826-835. https://doi.org/10.1038/nn.4004

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.

В: Nature Neuroscience, Том 18, № 6, 28.06.2015, стр. 826-835.

Результат исследований: Научные публикации в периодических изданияхстатья

TY - JOUR

T1 - Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease

AU - Laguna, Ariadna

AU - Schintu, Nicoletta

AU - Nobre, André

AU - Alvarsson, Alexandra

AU - Volakakis, Nikolaos

AU - Jacobsen, Jesper Kjaer

AU - Gómez-Galán, Marta

AU - Sopova, Elena

AU - Joodmardi, Eliza

AU - Yoshitake, Takashi

AU - Deng, Qiaolin

AU - Kehr, Jan

AU - Ericson, Johan

AU - Svenningsson, Per

AU - Shupliakov, Oleg

AU - Perlmann, Thomas

PY - 2015/6/28

Y1 - 2015/6/28

N2 - 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.

AB - 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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U2 - 10.1038/nn.4004

DO - 10.1038/nn.4004

M3 - Article

C2 - 25915474

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VL - 18

SP - 826

EP - 835

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 6

ER -

Laguna A, Schintu N, Nobre A, Alvarsson A, Volakakis N, Jacobsen JK и соавт. Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease. Nature Neuroscience. 2015 Июнь 28;18(6):826-835. https://doi.org/10.1038/nn.4004