A02:FAILURE of Bio-metal

A02:”Failure” of Bio-metal dynamics
Pathological Roles of Bio-metals in Human Diseases

It was shocking news to all of us that Professor Stephen Hawking passed away.  The disease from which he suffered for a long time is amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease. While we still do not have effective cures for ALS, it is getting clearer that bio-metals such as copper and zinc are abnormally accumulated in brain and spinal cord of patients with neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease as well as ALS. We thus suppose that “failure” of bio-metal dynamics is involved in pathogenesis of those neurodegenerative diseases; however, it still remains unclear how the failure causes the diseases.

A main purpose in A02 is to understand mechanisms of how bio-metal dynamics becomes abnormal in human diseases.  In particular, we will try to detect any abnormalities in the distribution of bio-metals in a tissue/cell using model mice and iPS cells of ALS.  We also examine pathological roles of Cu/Zn-superoxide dismutase (SOD1) in ALS and the other neurodegenerative disease.  Mutations in SOD1 gene have been known to cause familial forms of ALS, and recently, involvement of wild-type SOD1 in sporadic ALS is also proposed.  Furthermore, essential roles of iron in the virulence of infectious bacteria will be investigated in our project.  We hope our research can contribute to the development of cures for human diseases based upon bio-metals.

A02-1 Understanding a network of metallochaperones regulating intracellular copper dynamics
Leader Yoshiaki Furukawa(Keio University)
A02-2 生命金属動態の理解と制御のための分子認識素子の開発
Leader Kouhei Tsumoto(The University of Tokyo)
A02-3 Regulation of stem cell differentiation and growth processes viewing from biometal homeostasis and neurodegenerative diseases
Leader Isao Hozumi(Gifu Pharmaceutical University; Gifu University Hospital)