
The Library
An AMPK-dependent regulatory pathway in tau-mediated toxicity
Tools
Galasso, Alessia, Cameron, Charles S., Frenguelli, Bruno G. and Moffat, Kevin G. (2017) An AMPK-dependent regulatory pathway in tau-mediated toxicity. Biology Open, 6 (10). pp. 1434-1444. doi:10.1242/bio.022863 ISSN 2046-6390.
|
PDF
WRAP-AMPK-dependent-regulatory-pathway-tau-mediated-Frenguelli-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution. Download (1886Kb) | Preview |
|
![]() |
PDF
WRAP-AMPK-dependent-regulatory-pathway-tau-mediated-toxicity-Galasso-2017.pdf - Published Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (10Mb) |
Official URL: http://dx.doi.org/10.1242/bio.022863
Abstract
Neurodegenerative tauopathies are characterized by accumulation of hyperphosphorylated tau aggregates primarily degraded by autophagy.
The 5'AMP-activated protein kinase (AMPK) is expressed in most cells, including neurons. Alongside its metabolic functions, it is also known to be activated in Alzheimer's brains, phosphorylate tau and be a critical autophagy activator. Whether it plays a neurotoxic or neuroprotective role remains unclear. Complexly in tauopathies, while stress conditions can result in AMPK activation enhancing tau-mediated toxicity, AMPK activation is not always concomitant with autophagic induction.
Using a Drosophila in vivo quantitative approach, we have analysed the impact of AMPK and autophagy on tau-mediated toxicity, recapitulating the AMPK-mediated tauopathy condition: increased tau phosphorylation, without corresponding autophagy activation.
We have demonstrated that AMPK, binding to and phosphorylating tau at Ser-262, a site reported to facilitate soluble tau accumulation, affects its degradation. This phosphorylation results in exacerbation of tau toxicity and is ameliorated via rapamycin-induced autophagy stimulation.
Our findings support the development of combinatorial therapies effective at reducing tau toxicity targeting tau phosphorylation and AMPK-independent autophagic induction. The proposed in vivo tool represents an ideal readout to perform preliminary screening for drugs promoting this process.
Item Type: | Journal Article | ||||||||
---|---|---|---|---|---|---|---|---|---|
Subjects: | Q Science > QP Physiology | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Protein kinases, Microtubules, Drosophila, Cell death, Phosphorylation | ||||||||
Journal or Publication Title: | Biology Open | ||||||||
Publisher: | The Company of Biologists Ltd. | ||||||||
ISSN: | 2046-6390 | ||||||||
Official Date: | 15 October 2017 | ||||||||
Dates: |
|
||||||||
Volume: | 6 | ||||||||
Number: | 10 | ||||||||
Page Range: | pp. 1434-1444 | ||||||||
DOI: | 10.1242/bio.022863 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 18 August 2017 | ||||||||
Date of first compliant Open Access: | 21 August 2017 | ||||||||
Funder: | National Centre for the Replacement, Refinement, and Reduction of Animals in Research (Great Britain) (NC3R) | ||||||||
Grant number: | G0900801/91180 (NC3R) |
Request changes or add full text files to a record
Repository staff actions (login required)
![]() |
View Item |
Downloads
Downloads per month over past year