Axonal local translation and its implications in the pathogenesis of amyotrophic lateral sclerosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• Principal Investigator: Terenzio Marco 沖縄科学技術大学院大学, 分子神経科学ユニット, 准教授 (60867513)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ALS / motor neurons / LPS / biomarkers / hIPSC

Outline of Final Research Achievements

Our research aimed to understand ALS progression by deriving motor neurons (MNs) from ALS patient human pluripotent steam cells (hIPSCs), overcoming murine model limitations. Key achievements include:
1. Developing microfluidic chambers for axonal biology studies of MNs derived from ALS patients hIPSCs.　2. Enhancing MN differentiation yield from hIPSCs to over 70%.　3. Recapitulating ALS pathology, observing axonal degeneration, mitochondrial dysfunction, and protein aggregation in ALS MN cultures.　4. Identifying a mechanisms linking decrease in intracellular ATP levels to an increase of toxic TDP43 aggregation in ALS MNs.　5. Identifying potential ALS biomarkers from culture medium, with ongoing validation.

Free Research Field

Molecular Biology

Academic Significance and Societal Importance of the Research Achievements

ALS rapidly leads to death. Our research links mitochondrial defects and reduction of ATP, to cytoplasmic aggregates in motor neurons from ALS patients, expanding on the role of LPS in disease. We also identified possible biomarkers for diagnosis, to improve patients` treatment and quality of life.