Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau-Reference-Cited by-同舟云学术

Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau

Published:2020-11-20 Issue:6519 Volume:370 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Darwich Nabil F.¹^ORCID,Phan Jessica M.¹^ORCID,Kim Boram¹^ORCID,Suh EunRan²,Papatriantafyllou John D.³^ORCID,Changolkar Lakshmi²^ORCID,Nguyen Aivi T.¹^ORCID,O’Rourke Caroline M.¹,He Zhuohao²^ORCID,Porta Sílvia²^ORCID,Gibbons Garrett S.²^ORCID,Luk Kelvin C.²^ORCID,Papageorgiou Sokratis G.⁴^ORCID,Grossman Murray⁵^ORCID,Massimo Lauren⁵^ORCID,Irwin David J.⁵^ORCID,McMillan Corey T.⁵,Nasrallah Ilya M.⁶^ORCID,Toro Camilo⁷,Aguirre Geoffrey K.⁵^ORCID,Van Deerlin Vivianna M.²,Lee Edward B.¹^ORCID

Affiliation:

1. Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, PA, USA.

2. Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, PA, USA.

3. Medical Center of Athens, Memory Disorders Clinic and Day Care Center for Third Age “IASIS,” Athens, Greece.

4. First University Department of Neurology, Eginiteio University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

5. Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, PA, USA.

6. Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, PA, USA.

7. NIH Undiagnosed Diseases Program, National Human Genome Research Institute, MD, USA.

Abstract

Two ways to get tangled? Neurodegeneration in Alzheimer's disease dementia is associated with neurofibrillary tangles composed of aggregated tau protein. Darwich et al. describe an additional form of autosomal-dominant dementia with neurofibrillary tangles linked to a hypomorph mutation in valosin-containing protein (VCP). VCP was found to disaggregate pathologic tau, and the hypomorph mutation increased tau accumulation in cells and mice. These findings highlight the role of protein turnover in maintaining neuronal health and suggest that VCP may provide a therapeutic target for Alzheimer's disease. Science , this issue p. eaay8826

Funder

National Institutes of Health

NIH Office of the Director

BrightFocus Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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