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Dementia Research Project

Molecular mechanisms of neurodegenerative dementia

Project Leader Masato Hasegawa

Project Leader
Masato Hasegawa

Masato Hasegawa, the Head of Department of Brain and Neurosciences, studies the molecular pathogenesis and progression of neurodegenerative diseases. He started working on Alzheimer’s disease at Yasuo Ihara’s lab in 1988 where he identified phosphorylation and ubiquitination sites in tau. In 1995, he joined Michel Goedert’s lab at MRC LMB where he and others demonstrated that alpha-synuclein is the major component of filamentous inclusions in Parkinson’s disease and dementia with Lewy bodies. He next joined Takeshi Iwatsubo’s group in 1999 where he identified phosphorylation and ubiquitination of alpha-synuclein. In 2006, while at the Tokyo Metropolitan Institute of Psychiatry, he collaborated with Tetsuaki Arai and found that phosphorylated TDP-43 accumulates in frontotemporal dementias and amyotrophic lateral sclerosis. More recently, he has been studying the prion-like spread of neurodegenerative disease-associated proteins.

Backgrounds

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.

Objectives

  • 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

Members

Project Leader Masato Hasegawa

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