• Dementia Research Project

Dementia Research Project

Molecular mechanisms of neurodegenerative dementia

Project Leader Masato Hasegawa

Project Leader
Masato Hasegawa


In cells, ubiquitin governs the life and death of various proteins and cell organelles as a factor that determines their fate. In recent years, it has been suggested that ubiquitin abnormalities are closely related to various diseases including Parkinson’s.

This project, along with elucidating ubiquitin’s role in the body, which until now has been shrouded in mystery, seeks to reveal its association with neurodegenerative diseases such as Parkinson’s.


  • To perform neuropathological and biochemical analysis on post-mortem brain tissue to elucidate molecular pathogenesis
  • To create test tube, cellular, and animal models to reproduce patient pathologies and develop drugs and treatments that will be able to suppress the progression of disease
  • To elucidate the mechanisms of a propagation hypothesis proposed by the project team


Project Leader Masato Hasegawa

  • Takashi Nonaka
  • Genjiro Suzuki
  • Masami Suzukake
  • Yoshiki Takamatsu
  • Taeko Kimura

Selected Publications

  • Shimozawa A, Ono M, Takahara D, Tarutani A, Imura S, Masuda-Suzukake M, Higuchi M, Yanai K, Hisanaga SI, and Hasegawa M . (2017) “Propagation of pathological α-synuclein in marmoset brain.” Acta. Neuropathol. Commun. 5:12.
  • Hasegawa M, Nonaka T, and Masuda-Suzukake M. (2016) “α-Synuclein: Experimental Pathology.” Cold Spring Harb Perspect Med. 6. pii: a024273.
  • Tarutani A, Suzuki G, Shimozawa A, Nonaka T, Akiyama H, Hisanaga S, and Hasegawa M. (2016) “The Effect of Fragmented Pathogenic α-Synuclein Seeds on Prion-like Propagation.” J. Biol. Chem. 291:18675-18688.
  • Tanaka Y, Nonaka T, Suzuki G, Kametani F, and Hasegawa M. (2016) “Gain-of-function profilin 1 mutations linked to familial amyotrophic lateral sclerosis cause seed-dependent intracellular TDP-43 aggregation.” Hum. Mol. Genet. 25:1420-1433.
  • Shimonaka S, Nonaka T, Suzuki G, Hisanaga S, and Hasegawa M. (2016) “Templated Aggregation of TAR DNA-binding Protein of 43 kDa (TDP-43) by Seeding with TDP-43 Peptide Fibrils.” J. Biol. Chem. 291:8896-8907.
  • Taniguchi-Watanabe S, Arai T, Kametani F, Nonaka T, Masuda-Suzukake M, Tarutani A, Murayama S, Saito Y, Arima K, Yoshida M, Akiyama H, Robinson A, Mann D, Iwatsubo T, and Hasegawa M. (2016) “Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau.” Acta. Neuropathol. 131: 267-280.
  • Nonaka T, et al. Phosphorylation of TAR DNA-binding Protein of 43 kDa (TDP-43) by Truncated Casein Kinase 1 Triggers Mislocalization and Accumulation of TDP-43. J. Biol. Chem. 291: 5473-5483, 2016
  • Nonaka T, et al. Prion-like properties of pathological TDP-43 aggregates from diseased brains. Cell Rep. 4: 124-134 , 2013
  • Nonaka T, et al. Seeded aggregation and toxicity of alpha-synuclein and tau: cellular models of neurodegenerative diseases. J. Biol. Chem. 285: 34885-34898, 2010