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Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases.

Accepted version
Peer-reviewed

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Article

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Authors

Connolly, Niamh MC 
Theurey, Pierre 
Adam-Vizi, Vera 
Bazan, Nicolas G 
Bernardi, Paolo 

Abstract

Neurodegenerative diseases are a spectrum of chronic, debilitating disorders characterised by the progressive degeneration and death of neurons. Mitochondrial dysfunction has been implicated in most neurodegenerative diseases, but in many instances it is unclear whether such dysfunction is a cause or an effect of the underlying pathology, and whether it represents a viable therapeutic target. It is therefore imperative to utilise and optimise cellular models and experimental techniques appropriate to determine the contribution of mitochondrial dysfunction to neurodegenerative disease phenotypes. In this consensus article, we collate details on and discuss pitfalls of existing experimental approaches to assess mitochondrial function in in vitro cellular models of neurodegenerative diseases, including specific protocols for the measurement of oxygen consumption rate in primary neuron cultures, and single-neuron, time-lapse fluorescence imaging of the mitochondrial membrane potential and mitochondrial NAD(P)H. As part of the Cellular Bioenergetics of Neurodegenerative Diseases (CeBioND) consortium ( www.cebiond.org ), we are performing cross-disease analyses to identify common and distinct molecular mechanisms involved in mitochondrial bioenergetic dysfunction in cellular models of Alzheimer's, Parkinson's, and Huntington's diseases. Here we provide detailed guidelines and protocols as standardised across the five collaborating laboratories of the CeBioND consortium, with additional contributions from other experts in the field.

Description

Keywords

Animals, Humans, Mitochondria, Models, Biological, Neurodegenerative Diseases

Journal Title

Cell Death & Differentiation

Conference Name

Journal ISSN

1350-9047
1476-5403

Volume Title

25

Publisher

Nature Publishing Group
Sponsorship
Medical Research Council (MC_UU_00015/3)
Wellcome Trust (110159/Z/15/Z)
We acknowledge the support of the CeBioND EU Joint Programme for Neurodegenerative Disease Research (JPND; www.jpnd.eu). The programme is supported through the following national funding organisations: Canada, CIHR; Germany, BMBF; Ireland: Science Foundation Ireland (14/JPND/ B3077); Italy: MIUR; Sweden: VR.