Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7

Abstract c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and controls various physiological processes including apoptosis. A specific upstream activator of JNKs is the mitogen-activated protein kinase kinase 7 (MKK7). It has been reported that MKK7-JNK signal...

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Autores principales:	Tokiwa Yamasaki, Norie Deki-Arima, Asahito Kaneko, Norio Miyamura, Mamiko Iwatsuki, Masato Matsuoka, Noriko Fujimori-Tonou, Yoshimi Okamoto-Uchida, Jun Hirayama, Jamey D. Marth, Yuji Yamanashi, Hiroshi Kawasaki, Koji Yamanaka, Josef M. Penninger, Shigenobu Shibata, Hiroshi Nishina
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6a9368fbd39346199e31cb7fdeeb9f70
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spelling	oai:doaj.org-article:6a9368fbd39346199e31cb7fdeeb9f702021-12-02T12:32:30ZAge-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK710.1038/s41598-017-07845-x2045-2322https://doaj.org/article/6a9368fbd39346199e31cb7fdeeb9f702017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07845-xhttps://doaj.org/toc/2045-2322Abstract c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and controls various physiological processes including apoptosis. A specific upstream activator of JNKs is the mitogen-activated protein kinase kinase 7 (MKK7). It has been reported that MKK7-JNK signaling plays an important regulatory role in neural development, however, post-developmental functions in the nervous system have not been elucidated. In this study, we generated neuron-specific Mkk7 knockout mice (MKK7 cKO), which impaired constitutive activation of JNK in the nervous system. MKK7 cKO mice displayed impaired circadian behavioral rhythms and decreased locomotor activity. MKK7 cKO mice at 8 months showed motor dysfunctions such as weakness of hind-limb and gait abnormality in an age-dependent manner. Axonal degeneration in the spinal cord and muscle atrophy were also observed, along with accumulation of the axonal transport proteins JNK-interacting protein 1 and amyloid beta precursor protein in the brains and spinal cords of MKK7 cKO mice. Thus, the MKK7-JNK signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system.Tokiwa YamasakiNorie Deki-ArimaAsahito KanekoNorio MiyamuraMamiko IwatsukiMasato MatsuokaNoriko Fujimori-TonouYoshimi Okamoto-UchidaJun HirayamaJamey D. MarthYuji YamanashiHiroshi KawasakiKoji YamanakaJosef M. PenningerShigenobu ShibataHiroshi NishinaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tokiwa Yamasaki Norie Deki-Arima Asahito Kaneko Norio Miyamura Mamiko Iwatsuki Masato Matsuoka Noriko Fujimori-Tonou Yoshimi Okamoto-Uchida Jun Hirayama Jamey D. Marth Yuji Yamanashi Hiroshi Kawasaki Koji Yamanaka Josef M. Penninger Shigenobu Shibata Hiroshi Nishina Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7
description	Abstract c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and controls various physiological processes including apoptosis. A specific upstream activator of JNKs is the mitogen-activated protein kinase kinase 7 (MKK7). It has been reported that MKK7-JNK signaling plays an important regulatory role in neural development, however, post-developmental functions in the nervous system have not been elucidated. In this study, we generated neuron-specific Mkk7 knockout mice (MKK7 cKO), which impaired constitutive activation of JNK in the nervous system. MKK7 cKO mice displayed impaired circadian behavioral rhythms and decreased locomotor activity. MKK7 cKO mice at 8 months showed motor dysfunctions such as weakness of hind-limb and gait abnormality in an age-dependent manner. Axonal degeneration in the spinal cord and muscle atrophy were also observed, along with accumulation of the axonal transport proteins JNK-interacting protein 1 and amyloid beta precursor protein in the brains and spinal cords of MKK7 cKO mice. Thus, the MKK7-JNK signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system.
format	article
author	Tokiwa Yamasaki Norie Deki-Arima Asahito Kaneko Norio Miyamura Mamiko Iwatsuki Masato Matsuoka Noriko Fujimori-Tonou Yoshimi Okamoto-Uchida Jun Hirayama Jamey D. Marth Yuji Yamanashi Hiroshi Kawasaki Koji Yamanaka Josef M. Penninger Shigenobu Shibata Hiroshi Nishina
author_facet	Tokiwa Yamasaki Norie Deki-Arima Asahito Kaneko Norio Miyamura Mamiko Iwatsuki Masato Matsuoka Noriko Fujimori-Tonou Yoshimi Okamoto-Uchida Jun Hirayama Jamey D. Marth Yuji Yamanashi Hiroshi Kawasaki Koji Yamanaka Josef M. Penninger Shigenobu Shibata Hiroshi Nishina
author_sort	Tokiwa Yamasaki
title	Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7
title_short	Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7
title_full	Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7
title_fullStr	Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7
title_full_unstemmed	Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7
title_sort	age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase mkk7
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6a9368fbd39346199e31cb7fdeeb9f70
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Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7

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