A Genomic Screen for Modifiers of Tauopathy Identifies Puromycin-Sensitive Aminopeptidase as an Inhibitor of Tau-Induced Neurodegeneration

Karsten, S. L., Sang, T. K., Gehman, L. T., Chatterjee, S., Liu, J., Lawless, G. M., Sengupta, S., Berry, R. W., Pomakian, J., Oh, H. S., Schulz, C., Hui, K. S., Wiedau-Pazos, M., Vinters, H. V., Binder, L. I., Geschwind, D. H., Jackson, G. R. (2006) A Genomic Screen for Modifiers of Tauopathy Identifies Puromycin-Sensitive Aminopeptidase as an Inhibitor of Tau-Induced Neurodegeneration. Neuron, 51 (5). pp. 549-560. ISSN 08966273

URL: http://www.ncbi.nlm.nih.gov/pubmed/16950154
DOI: 10.1016/j.neuron.2006.07.019

Abstract

Neurofibrillary tangles (NFT) containing tau are a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD). NFT burden correlates with cognitive decline and neurodegeneration in AD. However, little is known about mechanisms that protect against tau-induced neurodegeneration. We used a cross species functional genomic approach to analyze gene expression in multiple brain regions in mouse, in parallel with validation in Drosophila, to identify tau modifiers, including the highly conserved protein puromycin-sensitive aminopeptidase (PSA/Npepps). PSA protected against tau-induced neurodegeneration in vivo, whereas PSA loss of function exacerbated neurodegeneration. We further show that human PSA directly proteolyzes tau in vitro. These data highlight the utility of using both evolutionarily distant species for genetic screening and functional assessment to identify modifiers of neurodegeneration. Further investigation is warranted in defining the role of PSA and other genes identified here as potential therapeutic targets in tauopathy. © 2006 Elsevier Inc. All rights reserved.

Item Type: Paper
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
diseases & disorders > nervous system diseases and disorders
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > neurofibrillary tangles
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > tau
CSHL Authors:
Communities: CSHL labs
Depositing User: CSHL Librarian
Date: 2006
Date Deposited: 14 Dec 2011 16:17
Last Modified: 01 Mar 2013 15:19
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22832

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