Quantitative Immunofluorescence Mapping of HSP70’s Neuroprotective Effects in FUS-ALS Mouse Models

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, often linked to mutations in the FUS gene, leading to toxic protein aggregates. This study investigates the role of HSP70, a molecular chaperone, in mitigating neurodegeneration in FUS-ALS mouse models. Using quantitativ...

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Main Authors: Gennadii A. Piavchenko, Ksenia S. Pokidova, Egor A. Kuzmin, Artem A. Venediktov, Ilya Y. Izmailov, Igor V. Meglinski, Sergey L. Kuznetsov
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Language:English
Published: MDPI AG 2024-12-01
Series:Applied Sciences
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Online Access:https://www.mdpi.com/2076-3417/14/24/11614
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author Gennadii A. Piavchenko
Ksenia S. Pokidova
Egor A. Kuzmin
Artem A. Venediktov
Ilya Y. Izmailov
Igor V. Meglinski
Sergey L. Kuznetsov
author_facet Gennadii A. Piavchenko
Ksenia S. Pokidova
Egor A. Kuzmin
Artem A. Venediktov
Ilya Y. Izmailov
Igor V. Meglinski
Sergey L. Kuznetsov
author_sort Gennadii A. Piavchenko
collection DOAJ
description Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, often linked to mutations in the FUS gene, leading to toxic protein aggregates. This study investigates the role of HSP70, a molecular chaperone, in mitigating neurodegeneration in FUS-ALS mouse models. Using quantitative immunofluorescence microscopy, we mapped cellular changes in the primary motor cortex of double transgenic FUS/HSP70 mice and compared them to single FUS-transgenic controls. Our results reveal that double transgenic mice exhibit significantly reduced neuronal damage and increased levels of mature neuronal (NeuN) and microglial (Iba1) markers, indicating a protective effect of HSP70. Intracellular HSP70 expression proved more effective than extracellular release, suggesting that targeted HSP70 delivery to neurons may offer a promising therapeutic avenue for ALS. This study underscores the potential of quantitative immunofluorescence for mapping neuroprotective pathways and highlights HSP70’s impact on mitigating FUS-related pathology in ALS.
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series Applied Sciences
spelling doaj-art-46cc431f3e9c42c6a09d86aa5a100da62024-12-27T14:07:50ZengMDPI AGApplied Sciences2076-34172024-12-0114241161410.3390/app142411614Quantitative Immunofluorescence Mapping of HSP70’s Neuroprotective Effects in FUS-ALS Mouse ModelsGennadii A. Piavchenko0Ksenia S. Pokidova1Egor A. Kuzmin2Artem A. Venediktov3Ilya Y. Izmailov4Igor V. Meglinski5Sergey L. Kuznetsov6Department of Human Anatomy and Histology, I. M. Sechenov First Moscow State Medical University (Sechenov University), 11/10, Mokhovaya Street, 125009 Moscow, RussiaDepartment of Human Anatomy and Histology, I. M. Sechenov First Moscow State Medical University (Sechenov University), 11/10, Mokhovaya Street, 125009 Moscow, RussiaDepartment of Human Anatomy and Histology, I. M. Sechenov First Moscow State Medical University (Sechenov University), 11/10, Mokhovaya Street, 125009 Moscow, RussiaDepartment of Human Anatomy and Histology, I. M. Sechenov First Moscow State Medical University (Sechenov University), 11/10, Mokhovaya Street, 125009 Moscow, RussiaDepartment of Human Anatomy and Histology, I. M. Sechenov First Moscow State Medical University (Sechenov University), 11/10, Mokhovaya Street, 125009 Moscow, RussiaDepartment of Human Anatomy and Histology, I. M. Sechenov First Moscow State Medical University (Sechenov University), 11/10, Mokhovaya Street, 125009 Moscow, RussiaDepartment of Human Anatomy and Histology, I. M. Sechenov First Moscow State Medical University (Sechenov University), 11/10, Mokhovaya Street, 125009 Moscow, RussiaAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, often linked to mutations in the FUS gene, leading to toxic protein aggregates. This study investigates the role of HSP70, a molecular chaperone, in mitigating neurodegeneration in FUS-ALS mouse models. Using quantitative immunofluorescence microscopy, we mapped cellular changes in the primary motor cortex of double transgenic FUS/HSP70 mice and compared them to single FUS-transgenic controls. Our results reveal that double transgenic mice exhibit significantly reduced neuronal damage and increased levels of mature neuronal (NeuN) and microglial (Iba1) markers, indicating a protective effect of HSP70. Intracellular HSP70 expression proved more effective than extracellular release, suggesting that targeted HSP70 delivery to neurons may offer a promising therapeutic avenue for ALS. This study underscores the potential of quantitative immunofluorescence for mapping neuroprotective pathways and highlights HSP70’s impact on mitigating FUS-related pathology in ALS.https://www.mdpi.com/2076-3417/14/24/11614heat shock proteinsHSP70HSPA1Aneurodegenerationprimary motor cortexamyotrophic lateral sclerosis
spellingShingle Gennadii A. Piavchenko
Ksenia S. Pokidova
Egor A. Kuzmin
Artem A. Venediktov
Ilya Y. Izmailov
Igor V. Meglinski
Sergey L. Kuznetsov
Quantitative Immunofluorescence Mapping of HSP70’s Neuroprotective Effects in FUS-ALS Mouse Models
Applied Sciences
heat shock proteins
HSP70
HSPA1A
neurodegeneration
primary motor cortex
amyotrophic lateral sclerosis
title Quantitative Immunofluorescence Mapping of HSP70’s Neuroprotective Effects in FUS-ALS Mouse Models
title_full Quantitative Immunofluorescence Mapping of HSP70’s Neuroprotective Effects in FUS-ALS Mouse Models
title_fullStr Quantitative Immunofluorescence Mapping of HSP70’s Neuroprotective Effects in FUS-ALS Mouse Models
title_full_unstemmed Quantitative Immunofluorescence Mapping of HSP70’s Neuroprotective Effects in FUS-ALS Mouse Models
title_short Quantitative Immunofluorescence Mapping of HSP70’s Neuroprotective Effects in FUS-ALS Mouse Models
title_sort quantitative immunofluorescence mapping of hsp70 s neuroprotective effects in fus als mouse models
topic heat shock proteins
HSP70
HSPA1A
neurodegeneration
primary motor cortex
amyotrophic lateral sclerosis
url https://www.mdpi.com/2076-3417/14/24/11614
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