ATP-dependent liquid phase separation during aging and neurodegeneration

2023 Fiscal Year Final Research Report

• 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
• Keywords: Neurodegeneration / Aging / ATP synthesis / Protein aggregation / Liquid phase separation

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

Free Research Field

Neuroscience

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