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Investigation of the role of exosome-mediated maintenance of proteostasis in neurodegenerative diseases.

Description: In this study, we investigated the role of exosome-mediated transmission of molecular chaperones on neurodegenerative diseases. We found that expression of molecular chaperones in peripheral tissues non-cell autonomously suppresses eye degeneration of polyglutamine disease model flies. By proteome analyses of blood exosomes of polyglutamine disease model mice and marmosets, we also discovered some biomarker candidates.

Funder: Japan Society for the Promotion of Science

Amount: ¥16,640,000

Funding type: research

Funder scheme: Grant-in-Aid for Scientific Research (B)

Start date: 2016-04-01

End date: 2019-03-31

Investigator: Yoshitaka Nagai

Institution: Osaka University

Funded outputs count: 24

Funder award ID: 16H05325

OpenAlex ID: G7490954812

Blood extracellular vesicles contribute to the exercise-mediated suppression of brain Aβ pathology in the App knockin mouse model of Alzheimer's disease

2026 · Akiko Takeda, Toshihide Takeuchi, et al. · Neurochemistry International · 4

Comparison of serum and plasma as a source of blood extracellular vesicles: Increased levels of platelet-derived particles in serum extracellular vesicle fractions alter content profiles from plasma extracellular vesicle fractions

2022 · Xiaoman Zhang, Toshihide Takeuchi, et al. · PLoS ONE · 95

Emerging roles of extracellular vesicles in polyglutamine diseases: Mutant protein transmission, therapeutic potential, and diagnostics

2022 · Toshihide Takeuchi, Yoshitaka Nagai · Neurochemistry International · 11

Structurally Distinct α‐Synuclein Fibrils Induce Robust Parkinsonian Pathology

2019 · Hideki Hayakawa, Rie Nakatani, et al. · Movement Disorders · 36

The lncRNA hsrω regulates arginine dimethylation of human FUS to cause its proteasomal degradation in Drosophila

2019 · Luca Lo Piccolo, Hideki Mochizuki, et al. · Journal of Cell Science · 28

Lipids as Trans-Acting Effectors for α-Synuclein in the Pathogenesis of Parkinson’s Disease

2019 · Kensuke Ikenaka, Mari Suzuki, et al. · Frontiers in Neuroscience · 20

Arylsulfatase A, a genetic modifier of Parkinson’s disease, is an α-synuclein chaperone

2019 · Jun Sung Lee, Kazuaki Kanai, et al. · Brain · 70

E46K mutant α-synuclein is more degradation resistant and exhibits greater toxic effects than wild-type α-synuclein in Drosophila models of Parkinson's disease

2019 · Ryusuke Sakai, Mari Suzuki, et al. · PLoS ONE · 14

Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid

2019 · Keita Kakuda, Kensuke Ikenaka, et al. · Scientific Reports · 43

Sleep Disturbance as a Potential Modifiable Risk Factor for Alzheimer’s Disease

2019 · Eiko N. Minakawa, Keiji Wada, et al. · International Journal of Molecular Sciences · 123

Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS

2018 · Yumiko Azuma, Takahiko Tokuda, et al. · Experimental Cell Research · 18

NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene

2018 · Itaru Yamamoto, Yumiko Azuma, et al. · Scientific Reports · 6

Supplemental Treatment for Huntington’s Disease with miR-132 that Is Deficient in Huntington’s Disease Brain

2018 · Masashi Fukuoka, Masaki Takahashi, et al. · Molecular Therapy — Nucleic Acids · 58

Pathological role of lipid interaction with α-synuclein in Parkinson's disease

2018 · Mari Suzuki, Kazunori Sango, et al. · Neurochemistry International · 68

Parkinson’s disease-linked DNAJC13 mutation aggravates alpha-synuclein-induced neurotoxicity through perturbation of endosomal trafficking

2018 · Shun Yoshida, Takafumi Hasegawa, et al. · Human Molecular Genetics · 56

Developing biomarkers for neurodegenerative diseases using genetically-modified common marmoset models

2018 · Ikuo Tomioka, Yoshitaka Nagai, et al. · Neural Regeneration Research · 6

FUS toxicity is rescued by the modulation of lncRNA hsrω expression in Drosophila melanogaster

2017 · Luca Lo Piccolo, Salinee Jantrapirom, et al. · Scientific Reports · 24

Generation of transgenic marmosets using a tetracyclin-inducible transgene expression system as a neurodegenerative disease model†

2017 · Ikuo Tomioka, Naotake Nogami, et al. · Biology of Reproduction · 43

Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine Diseases

2017 · Toshihide Takeuchi, Yoshitaka Nagai · Brain Sciences · 71

Chronic sleep fragmentation exacerbates amyloid β deposition in Alzheimer’s disease model mice

2017 · Eiko N. Minakawa, Koyomi Miyazaki, et al. · Neuroscience Letters · 59

Regulatory Role of RNA Chaperone TDP-43 for RNA Misfolding and Repeat-Associated Translation in SCA31

2017 · Taro Ishiguro, Nozomu Sato, et al. · Neuron · 138

Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms

2017 · Ikuo Tomioka, Hidetoshi Ishibashi, et al. · eNeuro · 86

Generation of a novel transgenic rat model for tracing extracellular vesicles in body fluids

2016 · Aya Yoshimura, Masaki Kawamata, et al. · Scientific Reports · 47

A small-angle X-ray scattering study of alpha-synuclein from human red blood cells

2016 · Katsuya Araki, Naoto Yagi, et al. · Scientific Reports · 44