Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration.

Research output: Contribution to journalArticle

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Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration. / Wiesner, Diana; Sinniger, Jérome; Henriques, Alexandre; Dieterlé, Stéphane; Müller, Hans-Peter; Rasche, Volker; Ferger, Boris; Dirrig-Grosch, Sylvie; Soylu, Rana; Petersén, Åsa; Walther, Paul; Linkus, Birgit; Kassubek, Jan; Wong, Philip C; Ludolph, Albert C; Dupuis, Luc.

In: Human Molecular Genetics, Vol. 24, No. 8, 2015, p. 2228-2240.

Research output: Contribution to journalArticle

Harvard

Wiesner, D, Sinniger, J, Henriques, A, Dieterlé, S, Müller, H-P, Rasche, V, Ferger, B, Dirrig-Grosch, S, Soylu, R, Petersén, Å, Walther, P, Linkus, B, Kassubek, J, Wong, PC, Ludolph, AC & Dupuis, L 2015, 'Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration.', Human Molecular Genetics, vol. 24, no. 8, pp. 2228-2240. https://doi.org/10.1093/hmg/ddu741

APA

Wiesner, D., Sinniger, J., Henriques, A., Dieterlé, S., Müller, H-P., Rasche, V., ... Dupuis, L. (2015). Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration. Human Molecular Genetics, 24(8), 2228-2240. https://doi.org/10.1093/hmg/ddu741

CBE

Wiesner D, Sinniger J, Henriques A, Dieterlé S, Müller H-P, Rasche V, Ferger B, Dirrig-Grosch S, Soylu R, Petersén Å, Walther P, Linkus B, Kassubek J, Wong PC, Ludolph AC, Dupuis L. 2015. Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration. Human Molecular Genetics. 24(8):2228-2240. https://doi.org/10.1093/hmg/ddu741

MLA

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Author

Wiesner, Diana ; Sinniger, Jérome ; Henriques, Alexandre ; Dieterlé, Stéphane ; Müller, Hans-Peter ; Rasche, Volker ; Ferger, Boris ; Dirrig-Grosch, Sylvie ; Soylu, Rana ; Petersén, Åsa ; Walther, Paul ; Linkus, Birgit ; Kassubek, Jan ; Wong, Philip C ; Ludolph, Albert C ; Dupuis, Luc. / Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration. In: Human Molecular Genetics. 2015 ; Vol. 24, No. 8. pp. 2228-2240.

RIS

TY - JOUR

T1 - Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration.

AU - Wiesner, Diana

AU - Sinniger, Jérome

AU - Henriques, Alexandre

AU - Dieterlé, Stéphane

AU - Müller, Hans-Peter

AU - Rasche, Volker

AU - Ferger, Boris

AU - Dirrig-Grosch, Sylvie

AU - Soylu, Rana

AU - Petersén, Åsa

AU - Walther, Paul

AU - Linkus, Birgit

AU - Kassubek, Jan

AU - Wong, Philip C

AU - Ludolph, Albert C

AU - Dupuis, Luc

PY - 2015

Y1 - 2015

N2 - Mutations in components of the molecular motor dynein/dynactin lead to neurodegenerative diseases of the motor system or atypical parkinsonism. These mutations are associated with prominent accumulation of vesicles involved in autophagy and lysosomal pathways, and with protein inclusions. Whether alleviating these defects would affect motor symptoms remain unknown. Here, we show that a mouse model expressing low levels of disease linked-G59S mutant dynactin p150(Glued) develops motor dysfunction >8 months before loss of motor neurons or dopaminergic degeneration is observed. Abnormal accumulation of autophagosomes and protein inclusions were efficiently corrected by lowering dietary protein content, and this was associated with transcriptional upregulations of key players in autophagy. Most importantly this dietary modification partially rescued overall neurological symptoms in these mice after onset. Similar observations were made in another mouse strain carrying a point mutation in the dynein heavy chain gene. Collectively, our data suggest that stimulating the autophagy/lysosomal system through appropriate nutritional intervention has significant beneficial effects on motor symptoms of dynein/dynactin diseases even after symptom onset.

AB - Mutations in components of the molecular motor dynein/dynactin lead to neurodegenerative diseases of the motor system or atypical parkinsonism. These mutations are associated with prominent accumulation of vesicles involved in autophagy and lysosomal pathways, and with protein inclusions. Whether alleviating these defects would affect motor symptoms remain unknown. Here, we show that a mouse model expressing low levels of disease linked-G59S mutant dynactin p150(Glued) develops motor dysfunction >8 months before loss of motor neurons or dopaminergic degeneration is observed. Abnormal accumulation of autophagosomes and protein inclusions were efficiently corrected by lowering dietary protein content, and this was associated with transcriptional upregulations of key players in autophagy. Most importantly this dietary modification partially rescued overall neurological symptoms in these mice after onset. Similar observations were made in another mouse strain carrying a point mutation in the dynein heavy chain gene. Collectively, our data suggest that stimulating the autophagy/lysosomal system through appropriate nutritional intervention has significant beneficial effects on motor symptoms of dynein/dynactin diseases even after symptom onset.

U2 - 10.1093/hmg/ddu741

DO - 10.1093/hmg/ddu741

M3 - Article

VL - 24

SP - 2228

EP - 2240

JO - Human Molecular Genetics

T2 - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 8

ER -