| Project/Area Number |
21K06400
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 46010:Neuroscience-general-related
|
|---|
| Research Institution | Okinawa Institute of Science and Technology Graduate University |
|---|
Principal Investigator |
Guillaud Laurent 沖縄科学技術大学院大学, 分子神経科学ユニット, グループリーダー (90596222)
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Project Status |
Completed (Fiscal Year 2023)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | Neurodegeneration / Aging / ATP synthesis / Protein aggregation / Liquid phase separation / ATP / Viscoelasticity / LPS / Mitochondria |
|---|
| Outline of Research at the Start |
My research proposal aims to elucidate the cellular mechanisms underlying protein LPS in neurons during our lifespan and in neurodegeneration such as in PD, AD or ALS. I will show that mitochondrial activity and the hydrotropic property of ATP are playing central roles in the regulation of protein solubility during aging, and that LPS are critical for the maintenance of cellular functions in healthy young neurons and are impaired in elder diseased neurons.
|
| Outline of Final Research Achievements |
My research project demonstrated the critical role of ATP hydrotropic activity in the regulation of cellular viscoelasticity and pathological protein aggregation during aging and in neurodegenerative diseases. My results indicated that the reduction in mitochondrial activity and ATP synthesis associated with aging and neurodegeneration lead to significant increase in protein aggregation and loss of axoplasmic viscoelasticity and can be rescued by boosting ATP synthesis via the NADH pathway. Altogether I show that preserving hight levels ATP throughout lifespan can reduce or alleviate the pathological aggregation of proteins in neurons and potentially protect against or slow down the progression or development of aged-related proteinopathies
|
| Academic Significance and Societal Importance of the Research Achievements |
My research achievements revealed the novel and critical hydrotropic function of ATP in the regulation of neuronal protein aggregation during aging and neurodegeneration. These results open the door to the development of new anti-aging and neuroprotective interventions
|
