Ito GentaFaculty of Pharmaceutical Sciences Associate Professor Graduate School of Pharmaceutical Sciences Associate Professor | ![]() |
I started my research in the pathobiochemistry of Parkinson's disease, a major neurodegenerative disease, in the laboratory of Professor Takeshi Iwatsubo (Graduate School of Pharmaceutical Sciences, The University of Tokyo). After working in the laboratories of Professor Dario Alessi (University of Dundee, Scotland) and Professor Taisuke Tomita (Graduate School of Pharmaceutical Sciences, The University of Tokyo). I moved to the laboratory of Professor Naoko Tate (Faculty of Pharmaceutical Sciences, Teikyo University) in 2021. I am still working on elucidating the pathogenic mechanism of Parkinson's and Alzheimer's diseases by analyzing the function and properties of proteins related to these diseases.
In particular, from the time I was a graduate student to the present, my research has focused on leucine-rich repeat kinase 2 (LRRK2) kinase (Ito et al, Biochemistry, 2006; Kamikawaji et al., Biochemistry, 2009; Ito and Iwatsubo, Biochem J, 2012; Kamikawaji et al., Biochemistry, 2013; Ito et al., PLOS One, 2014). It is a molecule that has been strongly suggested to play an important role in the pathogenesis of Parkinson's disease (PD), as it has been shown to be associated with the risk of developing not only familial PD with genetic mutations, but also sporadic PD in genome-wide association studies.
Although I have shown that LRRK2 phosphorylates several Rab proteins, vesicular transport-related small GTPases (Steger et al., eLife, 2016; Ito et al., Biochem J, 2016; Fan et al., Biochem J, 2018), the significance of phosphorylation in the regulation of Rab function and its role in the pathogenesis of PD remains unclear. Currently, I am working on the physiological function of LRRK2 (Araki et al., Hum Mol Genet, 2021), the mechanism by which abnormal activation of LRRK2 occurs in PD (Eguchi et al., PNAS, 2018; Ito-Nagai et al, JBC, 2022), and the resulting abnormal Rab protein phosphorylation cause neurodegeneration (Ito K et al., FASEB J, 2023; Ito G et al., BBRC, 2023).
Since moving to Teikyo University, I have also begun to use biochemical and physicochemical methods to elucidate the effects of amino acid D-isomerization on the pathogenesis of neurodegenerative diseases, which is the main research topic of our laboratory. Amino acid D-isomerization is a phenomenon that occurs non-enzymatically in amino acids including aspartic acid in vivo and increases with age. As such, it may trigger fibril formation of amyloid-β and tau proteins, which accumulate in the brain as amyloids in Alzheimer's disease.
Amino acid D-isomerization in proteins is ubiquitous in bacterial cell wall synthesis, but its role in higher organisms, the extent to which it occurs, and its physiological and pathological significance are completely unknown. I am working to develop a method to comprehensively analyze amino acid D-isomerization in proteins using proteomics techniques developed in my LRRK2 research.