Loss of nuclear REST/NRSF in aged-dopaminergic neurons in Parkinson's disease patients.
作者： Miwako Kawamura , Shigeto Sato , Gen Matsumoto , Takahiro Fukuda , Kahori Shiba-Fukushima
DOI: 10.1016/J.NEULET.2019.01.042
关键词: Parkinson's disease 、 Neuroscience 、 Dementia with Lewy bodies 、 Substantia nigra 、 Nucleus 、 Gene silencing 、 Biology 、 Neurodegeneration 、 Dopaminergic 、 Lewy body
摘要: Parkinson's disease (PD) is the second most common neurodegenerative disease. Lewy bodies and pale in dopaminergic neurons substantia nigra are pathological hallmarks of PD. A number diseases demonstrate aggregate formation, but how these aggregates associated with their pathogenesis remains unknown. It has been reported that repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) induced nuclei aged neurons, preserves neuronal function, protects against neurodegeneration during aging through repression cell death-inducing genes. The loss REST Alzheimer's pathology. However, its function Here we demonstrated enters nucleus neurons. On other hand, partially sequestrated mostly absent from brains PD dementia (DLB). Dopaminergic neuron-specific autophagy-deficient mice exhibit accumulation aggregates. Defects protein quality control system induce mRNA expression; gene product mainly appears Our results suggest pathology disturbs normal processes by sequestering may associate
sci-hub.se 参考文章(22)
Masaru Kurosawa, Gen Matsumoto, Hiroyuki Sumikura, Hiroyuki Hatsuta, Shigeo Murayama, Takashi Sakurai, Tomomi Shimogori, Nobutaka Hattori, Nobuyuki Nukina, Serine 403-phosphorylated p62/SQSTM1 immunoreactivity in inclusions of neurodegenerative diseases Neuroscience Research. ,vol. 103, pp. 64- 70 ,(2016) , 10.1016/J.NEURES.2015.08.002
Davide Schiffer, Valentina Caldera, Marta Mellai, Paola Conforti, Elena Cattaneo, Chiara Zuccato, Repressor element-1 silencing transcription factor (REST) is present in human control and Huntington's disease neurones. Neuropathology and Applied Neurobiology. ,vol. 40, pp. 899- 910 ,(2014) , 10.1111/NAN.12137
Maria Grazia Spillantini, Marie Luise Schmidt, Virginia M.-Y. Lee, John Q. Trojanowski, Ross Jakes, Michel Goedert, α-Synuclein in Lewy bodies Nature. ,vol. 388, pp. 839- 840 ,(1997) , 10.1038/42166
Kenji Kosaka, Shinsaku Oyanagi, Masaaki Matsushita, Akira Hori, Shoji Iwase, Presenile dementia with Alzheimer-, Pick- and Lewy-body changes. Acta Neuropathologica. ,vol. 36, pp. 221- 233 ,(1976) , 10.1007/BF00685366
Bushra Raj, Dave O'Hanlon, John P. Vessey, Qun Pan, Debashish Ray, Noel J. Buckley, Freda D. Miller, Benjamin J. Blencowe, Cross-regulation between an alternative splicing activator and a transcription repressor controls neurogenesis Molecular Cell. ,vol. 43, pp. 843- 850 ,(2011) , 10.1016/J.MOLCEL.2011.08.014
Y. Naruse, T. Aoki, T. Kojima, N. Mori, Neural restrictive silencer factor recruits mSin3 and histone deacetylase complex to repress neuron-specific target genes. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 96, pp. 13691- 13696 ,(1999) , 10.1073/PNAS.96.24.13691
Tao Lu, Liviu Aron, Joseph Zullo, Ying Pan, Haeyoung Kim, Yiwen Chen, Tun-Hsiang Yang, Hyun-Min Kim, Derek Drake, X. Shirley Liu, David A. Bennett, Monica P. Colaiácovo, Bruce A. Yankner, REST and stress resistance in ageing and Alzheimer’s disease Nature. ,vol. 507, pp. 448- 454 ,(2014) , 10.1038/NATURE13163
Gen Matsumoto, Koji Wada, Misako Okuno, Masaru Kurosawa, Nobuyuki Nukina, Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Molecular Cell. ,vol. 44, pp. 279- 289 ,(2011) , 10.1016/J.MOLCEL.2011.07.039
Masaaki Komatsu, Satoshi Waguri, Tomoki Chiba, Shigeo Murata, Jun-ichi Iwata, Isei Tanida, Takashi Ueno, Masato Koike, Yasuo Uchiyama, Eiki Kominami, Keiji Tanaka, Loss of autophagy in the central nervous system causes neurodegeneration in mice Nature. ,vol. 441, pp. 880- 884 ,(2006) , 10.1038/NATURE04723
C. Schoenherr, D. Anderson, The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science. ,vol. 267, pp. 1360- 1363 ,(1995) , 10.1126/SCIENCE.7871435