Neuropathology
Staff
| Prof. | Saito, Takashi, Ph.D |
|---|---|
| Lecturer | Kuwahara, Tomoki, Ph.D |
Overview
In this field, our primary research focus is on human neurodegenerative diseases, particularly Alzheimer’s disease and Parkinson’s disease, which are closely associated with the aging process of the brain. Our overarching goal is to elucidate the mechanisms underlying disease onset and progression, and to develop fundamental, disease-modifying therapies grounded in pathophysiology.
A hallmark of neurodegenerative diseases is the progressive neuronal cell death, which leads to irreversible impairment of brain function. In close association with this process, disease-specific accumulations of characteristic fibrillar proteins are observed both inside and outside degenerating neurons. These abnormally folded proteins undergo fibrillization and aggregation, resulting in cellular toxicity. Moreover, in a subset of hereditary cases, mutations in the genes encoding the constituent proteins of these aggregates are known to be directly linked to disease onset.
From this perspective, our research aims to clarify the molecular pathogenesis of neurodegeneration from both upstream (genetic factors) and downstream (accumulated proteins) directions. In addition, molecular alterations are thought to induce cellular dysfunction, which in turn disrupts intercellular communication within the brain and ultimately manifests as disease. Accordingly, we take a comprehensive approach to brain disorders by focusing not only on interactions between neurons and glial cells, but also on their interactions with peripheral organs and the immune system.
To address these issues, we currently focus its resources into five basic aims:
- Mechanisms of β-amyloid accumulation and clearance in the Alzheimer’s disease brain
- Studies on the accumulation and secretion of tau protein
- Regulation of brain pathology through interactions between central nervous system immunity (glial cells) and peripheral immunity (lymphocytes)
- Functional analysis of causative genes in Parkinson’s disease: studies on Lewy body constituent protein α-synuclein and the pathogenic kinase LRRK2
- Identification of surrogate biomarkers for predicting the onset of Alzheimer’s disease and evaluation of the efficacy of disease-modifying therapeutic agents
Contact
tsaito@m.u-tokyo.ac.jp