MAPT Mutations V337M and N297K Alter Organelle Trafficking in Frontotemporal Dementia Patient-Specific Motor Neurons

Author:

Hartmann Christiane1ORCID,Anskat Marie2,Ehrlich Marc3,Sterneckert Jared45ORCID,Pal Arun26,Hermann Andreas1278ORCID

Affiliation:

1. Translational Neurodegeneration Section “Albrecht Kossel”, Department of Neurology, University Medical Center Rostock, 18057 Rostock, Germany

2. Division for Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany

3. Novartis Pharma GmbH, 90429 Nuernberg, Germany

4. Center for Regenerative Therapies TU Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany

5. Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01069 Dresden, Germany

6. Dresden High Magnetic Field Laboratory (HLD-EMFL), Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany

7. Center for Transdisciplinary Neurosciences (CTNR), University Medical Center Rostock, 18057 Rostock, Germany

8. German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, 18147 Rostock, Germany

Abstract

Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by the progressive loss of neurons mainly in the frontal and temporal lobes of the brain. Mutations (e.g., V337M, N297K) in the microtubule-associated protein TAU (MAPT) are responsible 5–20% of familial FTD cases and have been associated with defects in organelle trafficking that plays a critical role in the proper function of cells, including transport of essential molecules and degradation of waste products. Due to the critical role of TAU mutations in microtubule stabilization and organelle transportation, it is of great interest to study these molecular mechanisms to develop effective therapeutic strategies. Therefore, herein, we analyzed mitochondrial and lysosomal trafficking in disease-specific spinal motor neurons by using live cell imaging in undirected (uncompartmentalized) and directed (compartmentalized) cell culture systems. While V337M neurons only expressed 3R TAU, the N297K mutant neurons expressed both 3R and 4R TAU. Axonal trafficking was affected differentially in V337M and N297 MAPT mutated neurons. These findings suggest that the MAPT mutations V337M and N297K impaired axon physiology differentially, which highlights the need for mutation- and/or 3R/4R TAU-specific therapeutic approaches.

Funder

Hermann und Lilly Schilling-Stiftung für medizinische Forschung im Stifterverband

NOMIS foundation

TU Dresden

Publisher

MDPI AG

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3