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.
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
2024.8.8
We have uncovered the molecular basis for the link between aging and neurodegenerative diseases, as explained by the nucleolar molecule PQBP3. The study was published online in the EMBO JOURNAL (press release).
2024.4.9
We elucidated the earliest developmental pathology of SCA1 using originally developed dynamic molecular network analyses, named 'iMAD', of sequentially acquired RNA-seq data during differentiation of SCA1 patient-derived iPSCs to Purkinje cells. The study has published online in Communications Biology (press release).
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).
We have uncovered the molecular basis for the link between aging and neurodegenerative diseases, as explained by the nucleolar molecule PQBP3. The study was published online in the EMBO JOURNAL (press release).
2024.4.9
We elucidated the earliest developmental pathology of SCA1 using originally developed dynamic molecular network analyses, named 'iMAD', of sequentially acquired RNA-seq data during differentiation of SCA1 patient-derived iPSCs to Purkinje cells. The study has published online in Communications Biology (press release).
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; Link) by 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.
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; Link) by 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).
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).
- PQBP3 prevents senescence by suppressing PSME3-mediated proteasomal Lamin B1 degradation
- Dynamic molecular network analysis of iPSC-Purkinje cells differentiation delineates roles of ISG15 in SCA1 at the earliest stage Abstract Journal
- AAV-mediated editing of PMP22 rescues Charcot-Marie-Tooth disease type 1A features in patient-derived iPS Schwann cells (2023)
- Antagonistic roles of canonical and Alternative-RPA in disease-associated tandem CAG repeat instability (2023)
- Mutant α-synuclein propagates via the lymphatic system of the brain in the monomeric state (2023)
- PQBP5/NOL10 maintains and anchors the nucleolus under physiological and osmotic stress conditions (2023)
- Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation (2021)
- HMGB1 signaling phosphorylates Ku70 and impairs DNA damage repair in Alzheimer’s disease pathology (2021)
- Prediction and verification of the AD-FTLD common pathomechanism based on dynamic molecular network analysis (2021)
- Hepta-Histidine Inhibits Tau Aggregation (2021)
- DNA damage in embryonic neural stem cell determines FTLDs’ fate via early-stage neuronal necrosis (2021)
- YAP-dependent necrosis occurs in early stages of Alzheimer's disease and regulates mouse model pathology (2020)
- The intellectual disability gene PQBP1 rescues Alzheimer’s disease pathology.
- Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-Aggregation Stage in PD/DLB Pathology
- Insights into familial middle-age dementia suggest new avenues for treatment (2018)
- Preclinical pathology during development affects the post-onset adulthood symptoms in spinocerebellar ataxia type 1 (2017)
- Starvation induced autophagy enhances accumulation of amyloid-beta (Aβ) in neurons (2015)
- Molecular basis for the earlist synapse pathology in preclinical Alzheimer's disease brain (2014)
- A molecular pathomechanism of microcephaly by mutations of PQBP1 gene (2014)
- VCP, a causative gene of FTLD controls the common pathology of polyglutamine diseases (2013)
- Intellectual disability gene PQBP1 affects lifespan (2012)
- A common mechanism underlying two polyglutamine diseases (~2011)