Department of Neuropathology

The goals of our department are to understand the mechanisms underlying neurodegenerative diseases and to develop effective therapeutics for such intractable disorders. At the present moment, Alzheimer’s disease, other dementias, polyglutamine diseases, and developmental disorders related to PQBP1 are the main targets of our laboratory. For more than 15 years, we have been focusing on the proteome and transcriptome analyses of cellular and animal models of Alzheimer's disease, FTLD, polyglutamine diseases and so on, and have obtained novel molecules that are critically involved in the pathomechanisms.

Especially, we proposed "DNA damage repair impairment" as a common pathology across multiple neurodegenerative diseasese, and proposed "intracellular amyloid hypothesis" and "ultra-early phase pathology hypothesis" as new concepts that might replace previous "amyloid hypothesis" and provide a new orientation to develop radical therapy against Alzheimer's disease.

We are now reaching to the stage to develop our research results to clinical application.

News & Topics

2024.3.24
We have published a review article on various subtypes of necrosis, including our newly discovered necrosis named TRIAD, and their relationship to neurodegeneration and neuroinflammation (link).
 
2023.12.21
Our recent paper on the development of genome editing gene therapy for Charcot-Marie-Tooth disease was ranked third out of all research papers in Communications Medicine's "Trending - Altmetric" (screenshot).

2023.12.19
One of the authors of our recent paper in Communications Medicine, Juliana Bosso Taniguchi, who is also a graduate of our laboratory, was featured on the website of the University of Passo Fundo in Brazil, where she is currently affiliated (Link; in Portuguese).

2023.11.28
We have developed a new gene therapy method of Charcot-Marie-Tooth disease type 1A (CMT1A) using genome editing to PMP22 gene. The study has published online in Communications Medicine, a new international journal that is publised by Nature Portfolio.(press release

2023.10.26
An introductory article of our research paper about α-synuclein was published online in "Science Japan" (English; Link) and "客観日本" (Chinese; Linkby Japan Science and Technology Agency (JST).

2023.10.11
The results of our joint research with Prof.Pearson of the university of Toronto were published online in Cell.
RpA1 is one of the promising theraputic target molecule of spinocerebellar ataxia 1 (SCA1; Taniguchi et al, Hum Mol Genet 2016) that had been found by us (Barclay et al, Hum Mol Genet 2013). In this research, we have elucidated more detailed mechanism. As a result, the potential of realizing gene therapy for CAG triplet repeat diseases has increased(Link).


2023.9.11
Our research paper about lymphatic propagation of α-synuclein was introduced in Nature Reviews Neurology(Link).

2023.8.17
We have shown that a mutated version of a protein called α-synuclein propagates to various cerebral regions through the lymphatic system and then aggregates. The study has published online in Cell Reports (press release).

2023.4.13
Our collaborative research work with Dr. Shiwaku has published online in Brain, Behavior, and Immunity (press release).

2023.1.4
We have revealed that an intrinsically disordered protein (IDP), named PQBP5, is crucial for the stability of an organelle called the nucleolus. This finding leads not only to an understanding of the nature of living cells, but also to the opening up of possibilities to control cancer, senescence, or neurodegeneration in the future.
The study published in Nature Communications is available online (press release).

2023.1.3
Prof. Okazawa joined a discussion about the latest research topics in 
Alzheimer's disease (AD) pathology in Alzforum (link), in which Prof. Okazawa discussed with the authors about the relationship between three models of ultra-early stage AD pathologies before amyloid plaque formation, TRIAD, PANTHOS and PAAS.

TRIAD was found by Prof. Okazawa at 2006(Hoshino et al, JCB 2006) and 
determined as a main type of neuronal necrosis from the early to late stage of AD (Fujita et al, Sci 
Rep 2016; Tanaka et al, Nature Commun 2020; Tanaka et al, Commun Biol 2021). PANTHOS was reported in 2022 by a research group led by Prof. Nixon in USA(Nature Neurosci 2022). PAAS was reported recently by a research group led by Prof. Grutzendler in USA(Nature 2022).

These new AD pathologies preceding extracellular deposition of 
Amyloid-beta are drawing attention of AD researchers and ordinary people in the society.

 
2022.12.8
Prof. Okazawa gave an invited lecture at the 51st annual meeting of the Japanese society for immunology on innate immune function in neurodegenerative diseases such as Alzheimer's disease (program).

2022.7.1
Prof. Okazawa joined a discussion about the latest research topics in 
Alzheimer's disease (AD) pathology in Alzforum (link), in which Prof. Okazawa discussed with the authors about the relationship between two models of ultra-early stage AD pathologies before amyloid plaque formation, TRIAD and PANTHOS.

TRIAD was found by Prof. Okazawa at 2006(Hoshino et al, JCB 2006) and 
determined as a main type of neuronal necrosis from the early to late stage of AD (Fujita et al, Sci 
Rep 2016; Tanaka et al, Nature Commun 2020; Tanaka et al, Commun Biol 2021). PANTHOS was reported recently by a research group led by Prof. Nixon in USA(Nature Neurosci 2022).

These new AD pathologies preceding extracellular deposition of 
Amyloid-beta are drawing attention of AD researchers and ordinary people in the society.

2022.6.2
A review article about an intellectual disability causative gene PQBP1, discovered by our research group, was published online.

2022.4.20
Our collaborative research work with Dr. Shiwaku has published online in Cell Reports Medicine (press release).