Neurology
Principal Investigator:
Shinji Saiki
E-mail.address: ssaiki@md.tsukuba.ac.jp
URL: https://neurology.md.tsukuba.ac.jp
Other Faculty Members

Assistant Professor: Kiyotaka Nakamagoe: nakamagoek@md.tsukuba.ac.jp
Assistant Professor: Yasushi Tomidokoro: tomidy01@md.tsukuba.ac.jp
Assistant Professor: Ayako Shioya: ayshioya@md.tsukuba.ac.jp
Assistant Professor: Motoki Fujimaki: mtfujima@md.tsukuba.ac.jp
Assistant Professor: Tetsushi Kataura: tkataura@md.tsukuba.ac.jp

Major Scientific Interests of the GroupWe explore biomarkers and treatments for Parkinson’s disease, other neurodegenerative diseases,
and REM sleep behaviour disorder using state-of-the-art multi-omic analyses. We have revealed
alterations in fatty acid β-oxidation, polyamine and caffeine metabolism as well as changes insebum mRNA in Parkinson’s disease. Based on these findings, we develop a) new methods forearly diagnosis and treatment evaluation, b) mechanistic understanding of the pathology and c)
drug candidates for disease-modifying therapy. In this context, our particular interest is autophagy,
an intracellular degradation system mediated by sequestration of cellular components into
autophagosomes, followed by lysosomal degradation. Compromised autophagy has been
implicated in the pathology of myriad human disorders including neurodegenerative diseases, andthereby restoring autophagic capacity is a promising therapeutic strategy. We investigate, in thecontext of neurodegenerative diseases, a) how autophagy is impaired, b) how autophagy
dysfunction determines cell fate (such as apoptosis, ferroptosis and senescence), and c) develop
small molecules to combat these diseases, using molecular cell biology techniques.
Projects for Regular Students in Doctoral or Master’s Programs
1) Presymptomatic physiological biomarker identification for Parkinson’s disease.
2) Liquid biomarker identification for Parkinson’s disease and REM sleep behaviour disorder.
3) Mechanisms and treatments of Parkinson’s and rare neurodegenerative diseases.
4) Mechanisms and interventions of ageing, the biggest risk factor of neurodegenerative diseases.
Study Programs for Short Stay Students (one week – one semester)1) Autophagy flux assay to monitor autophagic activity in cultured cells.
2) Various cell death assays to evaluate cytotoxicity, apoptosis or ferroptosis in neuronal cells.

Selected Publications

1) Kelly G† & Kataura T† et al., Suppressed basal mitophagy drives cellular ageing phenotypes which canbe reversed by a p62-targeting small molecule. Developmental Cell (in press).
2) Date Y et al. & Saiki S*, Novel autophagy inducers by accelerating lysosomal clustering against
Parkinson's disease. eLife 13:e98649 (2024).
3) Kataura T†* & Sedlackova† L et al., Targeting the autophagy-NAD axis protects against cell death inNiemann-Pick type C1 disease models. Cell Death & Disease 15(5):382 (2024).
4) Zhu Y† & Fujimaki M† et al., Loss of WIPI4 in neurodegeneration causes autophagy-independentferroptosis. Nature Cell Biology 26(4):542-551 (2024).

5) Miyamoto K, Saiki S* et al., Systemic metabolic alteration dependent on the thyroid-liver axis in early
PD. Annals of Neurology 93:303-316 (2023).
6) Kataura T et al., NDP52 acts as a redox sensor in PINK1/Parkin-mediated mitophagy. EMBO Journal
42: e111372 (2023).
7) Sasazawa Y et al. & Saiki S*. Oxidative stress-induced phosphorylation of JIP4 regulates lysosomal
positioning in coordination with TRPML1 and ALG2. EMBO Journal 41:e111476 (2022).
8) Kataura T† Sedlackova L† et al., Autophagy promotes cell survival by maintaining NAD levels.
Developmental Cell 57:2584-2598 (2022).
9) Kataura T et al., A chemical genomics-aggrephagy integrated method studying functional analysis ofautophagy inducers. Autophagy 17:1856-1872 (2021).
10) Saiki S†* & Sasazawa Y† et al., A metabolic profile of polyamines in Parkinson’s disease: a promisingbiomarker. Annals of Neurology 86:251-263 (2019).
11) Fujimaki M et al., Iron Supply via NCOA4-Mediated Ferritin Degradation Maintains MitochondrialFunctions. Molecular and Cellular Biology, 39(14): e00010-19 (2019).
12) Fujimaki M, Saiki S* et al., Serum caffeine and metabolites are reliable biomarkers of early Parkinson’sdisease. Neurology 90:e404-e411 (2018).
13) Korolchuk VI† & Saiki S† et al., Lysosomal positioning coordinates cellular nutrient responses. NatureCell Biology 13:453-60 (2011).
14) Saiki S, et al., Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K
inhibition. Autophagy 7:176-87 (2011).