Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease

Among all the proposed pathogenic mechanisms to understand the etiology of Alzheimer’s disease (AD), increased oxidative stress seems to be a robust and early disease feature where many of those hypotheses converge. However, despite the significant lines of evidence accumulated, an effective diagnos...

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Main Authors: Laura Gómez-Virgilio, Alejandro Luarte, Daniela P. Ponce, Bárbara A. Bruna, María I. Behrens
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/12/6311
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author Laura Gómez-Virgilio
Alejandro Luarte
Daniela P. Ponce
Bárbara A. Bruna
María I. Behrens
author_facet Laura Gómez-Virgilio
Alejandro Luarte
Daniela P. Ponce
Bárbara A. Bruna
María I. Behrens
author_sort Laura Gómez-Virgilio
collection DOAJ
description Among all the proposed pathogenic mechanisms to understand the etiology of Alzheimer’s disease (AD), increased oxidative stress seems to be a robust and early disease feature where many of those hypotheses converge. However, despite the significant lines of evidence accumulated, an effective diagnosis and treatment of AD are not yet available. This limitation might be partially explained by the use of cellular and animal models that recapitulate partial aspects of the disease and do not account for the particular biology of patients. As such, cultures of patient-derived cells of peripheral origin may provide a convenient solution for this problem. Peripheral cells of neuronal lineage such as olfactory neuronal precursors (ONPs) can be easily cultured through non-invasive isolation, reproducing AD-related oxidative stress. Interestingly, the autofluorescence of key metabolic cofactors such as reduced nicotinamide adenine dinucleotide (NADH) can be highly correlated with the oxidative state and antioxidant capacity of cells in a non-destructive and label-free manner. In particular, imaging NADH through fluorescence lifetime imaging microscopy (FLIM) has greatly improved the sensitivity in detecting oxidative shifts with minimal intervention to cell physiology. Here, we discuss the translational potential of analyzing patient-derived ONPs non-invasively isolated through NADH FLIM to reveal AD-related oxidative stress. We believe this approach may potentially accelerate the discovery of effective antioxidant therapies and contribute to early diagnosis and personalized monitoring of this devastating disease.
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spelling doaj.art-0359b599071f425e9ebc08103f2670dd2023-11-21T23:50:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012212631110.3390/ijms22126311Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s DiseaseLaura Gómez-Virgilio0Alejandro Luarte1Daniela P. Ponce2Bárbara A. Bruna3María I. Behrens4Centro de Investigación Clínica Avanzada, Facultad de Medicina and Hospital Clínico Universidad de Chile, Santiago 8380453, CP, ChileCentro de Investigación Clínica Avanzada, Facultad de Medicina and Hospital Clínico Universidad de Chile, Santiago 8380453, CP, ChileCentro de Investigación Clínica Avanzada, Facultad de Medicina and Hospital Clínico Universidad de Chile, Santiago 8380453, CP, ChileCentro de Investigación Clínica Avanzada, Facultad de Medicina and Hospital Clínico Universidad de Chile, Santiago 8380453, CP, ChileCentro de Investigación Clínica Avanzada, Facultad de Medicina and Hospital Clínico Universidad de Chile, Santiago 8380453, CP, ChileAmong all the proposed pathogenic mechanisms to understand the etiology of Alzheimer’s disease (AD), increased oxidative stress seems to be a robust and early disease feature where many of those hypotheses converge. However, despite the significant lines of evidence accumulated, an effective diagnosis and treatment of AD are not yet available. This limitation might be partially explained by the use of cellular and animal models that recapitulate partial aspects of the disease and do not account for the particular biology of patients. As such, cultures of patient-derived cells of peripheral origin may provide a convenient solution for this problem. Peripheral cells of neuronal lineage such as olfactory neuronal precursors (ONPs) can be easily cultured through non-invasive isolation, reproducing AD-related oxidative stress. Interestingly, the autofluorescence of key metabolic cofactors such as reduced nicotinamide adenine dinucleotide (NADH) can be highly correlated with the oxidative state and antioxidant capacity of cells in a non-destructive and label-free manner. In particular, imaging NADH through fluorescence lifetime imaging microscopy (FLIM) has greatly improved the sensitivity in detecting oxidative shifts with minimal intervention to cell physiology. Here, we discuss the translational potential of analyzing patient-derived ONPs non-invasively isolated through NADH FLIM to reveal AD-related oxidative stress. We believe this approach may potentially accelerate the discovery of effective antioxidant therapies and contribute to early diagnosis and personalized monitoring of this devastating disease.https://www.mdpi.com/1422-0067/22/12/6311oxidative stressFLIMAlzheimer’s disease
spellingShingle Laura Gómez-Virgilio
Alejandro Luarte
Daniela P. Ponce
Bárbara A. Bruna
María I. Behrens
Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease
International Journal of Molecular Sciences
oxidative stress
FLIM
Alzheimer’s disease
title Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease
title_full Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease
title_fullStr Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease
title_full_unstemmed Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease
title_short Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease
title_sort analyzing olfactory neuron precursors non invasively isolated through nadh flim as a potential tool to study oxidative stress in alzheimer s disease
topic oxidative stress
FLIM
Alzheimer’s disease
url https://www.mdpi.com/1422-0067/22/12/6311
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