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Understanding the pathophysiological actions of tau oligomers : a critical review of current electrophysiological methods

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Hill, Emily, Wall, Mark J., Moffat, Kevin G. and Karikari , T. (2020) Understanding the pathophysiological actions of tau oligomers : a critical review of current electrophysiological methods. Frontiers in Molecular Neuroscience, 13 . 155. doi:10.3389/fnmol.2020.00155

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Official URL: https://doi.org/10.3389/fnmol.2020.00155

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Abstract

Tau is a predominantly neuronal protein that is normally bound to microtubules, where it acts to modulate neuronal and axonal stability. In humans, pathological forms of tau are implicated in a range of diseases that are collectively known as tauopathies. Kinases and phosphatases are responsible for maintaining the correct balance of tau phosphorylation to enable axons to be both stable and labile enough to function properly. In the early stages of tauopathies, this balance is interrupted leading to dissociation of tau from microtubules. This leaves microtubules prone to damage and phosphorylated tau prone to aggregation. Initially, phosphorylated tau forms oligomers, then fibrils, and ultimately neurofibrillary tangles (NFTs). It is widely accepted that the initial soluble oligomeric forms of tau are probably the most pathologically relevant species but there is relatively little quantitative information to explain exactly what their toxic effects are at the individual neuron level. Electrophysiology provides a valuable tool to help uncover the mechanisms of action of tau oligomers on synaptic transmission within single neurons. Understanding the concentration-, time-, and neuronal compartment-dependent actions of soluble tau oligomers on neuronal and synaptic properties are essential to understanding how best to counteract its effects and to develop effective treatment strategies. Here, we briefly discuss the standard approaches used to elucidate these actions, focusing on the advantages and shortcomings of the experimental procedures. Subsequently, we will describe a new approach that addresses specific challenges with the current methods, thus allowing real-time toxicity evaluation at the single-neuron level.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history
Q Science > QP Physiology
Divisions: Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Oligomers , Neurons , Electrophysiology
Journal or Publication Title: Frontiers in Molecular Neuroscience
Publisher: Frontiers Research Foundation
ISSN: 1662-5099
Official Date: 2020
Dates:
DateEvent
2020Published
20 August 2020Available
28 July 2020Accepted
Date of first compliant deposit: 28 July 2020
Volume: 13
Article Number: 155
DOI: 10.3389/fnmol.2020.00155
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIED[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDBrightFocus Foundationhttp://dx.doi.org/10.13039/100006312
AF-930627Alzheimerfondenhttp://dx.doi.org/10.13039/501100008599
FO2020-0240Hjärnfondenhttps://www.hjarnfonden.se/
UNSPECIFIEDDemensförbundethttp://dx.doi.org/10.13039/100010773
UNSPECIFIEDAgneta Prytz-Folkes och Gösta Folkes Stiftelsehttp://dx.doi.org/10.13039/501100007484
UNSPECIFIEDStiftelsen för Gamla Tjänarinnorhttp://dx.doi.org/10.13039/100010815
UNSPECIFIEDAlex och Eva Wallströms Stiftelse för Vetenskaplig Forskning och Utbildninghttp://dx.doi.org/10.13039/501100009734
UNSPECIFIEDGun och Bertil Stohnes Stiftelsehttp://dx.doi.org/10.13039/100009673
UNSPECIFIEDAnna-Lisa och Bror Björnssons stiftelsehttps://bjornssonsstiftelse.se/
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