The role of TTYH1 in glial cell autophagy

TTYH1在胶质细胞自噬中的作用

基本信息

  • 批准号:
    10666127
  • 负责人:
  • 金额:
    $ 15.7万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-06-01 至 2025-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary Tweety Homolog 1 (TTYH1) is an understudied protein identified by the Illuminating the Druggable Genome (IDG) Program. Our current knowledge on TTYH1 is limited to its involvement in neural stem cell development and glioma invasion. Given the lack of model system and genetic tools, molecular function and biological pathways that are associated with TTYH1 remain poorly defined. Importantly, altered expression levels of TTYH1 have been found in brain samples from Alzheimer’s disease and Parkinson’s disease patients. Therefore, elucidating the functional roles of TTYH1 in brain cells will aid in the understanding of disease pathogenesis. We performed transcriptomic analyses and determined that TTYH1 is predominantly expressed in brain astrocytes. Astrocytes are glial cells responsible for processing lipids and providing metabolic support to neurons. In Drosophila glia, immortalized rat astrocytes, and primary human astrocytes, we found that TTYH1 orthologs are localized to lysosome, the organelle required for performing autophagy. Indeed, we found that TTYH1 facilitates autophagic flux in glial cells. Delineating the mechanistic underpinnings of autophagy regulation will uncover the molecular function and biological role of TTYH1. Our data suggest that defective clearance of internalized sphingolipids underlies lysosomal dysfunction and diminished autophagy in TTYH1- deficient glial cells. The preliminary findings inform our central hypothesis that TTYH1 mediates lysosomal clearance of sphingolipids to facilitate autophagy. To test our working hypothesis, we will leverage rat astrocytic cell model and Drosophila model combined with tools and experimental paradigms developed for this project. At the conclusion of this investigation, we will have furthered our understanding of the molecular function of TTYH1 in glial lipid metabolism. Findings from this project will also offer insights to understanding lysosomal storage diseases and neurodegeneration.
项目总结

项目成果

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Ching-On Wong其他文献

Ching-On Wong的其他文献

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{{ truncateString('Ching-On Wong', 18)}}的其他基金

Role of TTYH1 in mobilizing lipids and ApoE in glia: Implications for brain aging and neurodegeneration
TTYH1 在神经胶质细胞动员脂质和 ApoE 中的作用:对大脑衰老和神经退行性变的影响
  • 批准号:
    10644705
  • 财政年份:
    2023
  • 资助金额:
    $ 15.7万
  • 项目类别:
Regulation of Apolipoprotein Secretion by TTYH1 and tweety in Glial Cells
胶质细胞中 TTYH1 和 tweety 对载脂蛋白分泌的调节
  • 批准号:
    10085308
  • 财政年份:
    2019
  • 资助金额:
    $ 15.7万
  • 项目类别:
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