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Brain Pathology

Laboratory of Structural Neuropathology

Nobuyuki Nukina,Ph.D.,M.D.
Nobuyuki Nukina,Ph.D.,M.D.
The pathomechanism of neurodegenerative disorders are not fully elucidated yet. The responsible genes for hereditary neurodegenerative diseases have been identified by the genetic approach and many of those diseases showed the accumulation of their gene products in neurons. In Huntington disease and hereditary spinocerebellar ataxias, expanded polyglutamine accumulates and forms aggregates in neuronal nuclei. We are studying the pathological process in which the mutation induced the misfolding of the gene product and the misfolded gene product accumulates and induces neuronal degeneration, using cell biological and structural biological approach. We are searching for the protecting factors and compounds for those pathological processes and chaperones and ubiquitin-proteasome pathway are important factors for the folding and degradation of misfolding proteins. We are also investigating other neurodegenerative disorders such as synucleinopathy and tauopathy, which are induced by misfolded proteins and show dementia. In addition, we recently identified large bundles of unmyelinated fibers in basal ganglia and are studying the physiological and pathological roles of unmyelinated fibers in central nervous system. Our goal is to protect the conformational diseases induced by protein misfolding.

Research topics

  1. The mechanism of aggregation formation of misfolded proteins
  2. Protein quality control in cells
  3. Physiological and pathological roles of unmyelinated fibers in the central nervous systems

Selected publications

  1. Yamanaka T, Tosaki A, Miyazaki H, Kurosawa M, Koike M, Uchiyama Y, Maity SN, Misawa H, Takahashi R, Shimogori T, Hattori N, Nukina N. Differential roles of NF-Y transcription factor in ER chaperone expression and neuronal maintenance in the CNS. Sci Rep. 2016;6:34575.
  2. Shimizu H, Miyazaki H, Ohsawa N, Shoji S, Ishizuka-Katsura Y, Tosaki A, Oyama F, Terada T, Sakamoto K, Shirouzu M, Sekine S, * Nukina N , *Yokoyama S. Structure-based site-directed photo-crosslinking analyses of multimeric cell-adhesive interactions of voltage-gated sodium channel β subunits. Sci Rep. 2016;6:26618. *co-correspondence
  3. Miyazaki H, Oyama F, Inoue R, et al. Singular localization of sodium channel beta4 subunit in unmyelinated fibres and its role in the striatum. Nat Commun. 2014;5:5525.
  4. Yamanaka T, Tosaki A, Kurosawa M, et al. NF-Y inactivation causes atypical neurodegeneration characterized by ubiquitin and p62 accumulation and endoplasmic reticulum disorganization. Nat Commun. 2014;5:3354.
  5. Matsumoto G, Wada K, Okuno M, et al. Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Mol Cell. 2011;44(2):279-89.
  6. Bauer PO, Goswami A, Wong HK, et al. Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein. Nat Biotechnol. 2010;28(3):256-63.
  7. Furukawa Y, Kaneko K, Matsumoto G, et al. Cross-seeding fibrillation of Q/N-rich proteins offers new pathomechanism of polyglutamine diseases. J Neurosci. 2009;29(16):5153-62.
  8. Yamanaka T, Miyazaki H, Oyama F, et al. Mutant Huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factor. EMBO J. 2008;27(6):827-39.
  9. Sakurai T, Kaneko K, Okuno M, et al. Membrane microdomain switching: a regulatory mechanism of amyloid precursor protein processing. The Journal of cell biology. 2008;183(2):339-52.
  10. Tanaka M, Machida Y, Niu S, et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med. 2004;10(2):148-54.


Nobuyuki Nukina Ph.D., M.D. (Principal investigator, Professor)
Tomoyuki Yamanaka, Ph.D. (Research associate professor)
Haruko Miyazaki, Ph.D. (Research assistant professor)
Yukie Sekikawa (Secretary)


4F Hochikan, 1-3 Tatara Miyakodani, Kyotanabe-shi, Kyoto 610‐0394 Japan
Telephone : +81-774-65-7212
E-mail : nnukina@mail.doshisha.ac.jp