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

Gennadii A. Piavchenko; Ksenia S. Pokidova; Egor A. Kuzmin; Artem A. Venediktov; Ilya Y. Izmailov; Igor V. Meglinski; Sergey L. Kuznetsov

doi:10.3390/app142411614

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

Gennadii A. Piavchenko, Ksenia S. Pokidova, Egor A. Kuzmin, Artem A. Venediktov, Ilya Y. Izmailov, Igor V. Meglinski, Sergey L. Kuznetsov

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	11614
Number of pages	14
Journal	Applied Sciences
Volume	14
Issue number	24
Early online date	12 Dec 2024
DOIs	https://doi.org/10.3390/app142411614
Publication status	Published - Dec 2024

Bibliographical note

Copyright © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Keywords

heat shock proteins
HSP70
HSPA1A
neurodegeneration
primary motor cortex
amyotrophic lateral sclerosis
ALS
fused in sarcoma
FUS
transgenic animals
immunofluorescence
microscopy

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GA Piavchenko et al_Quantitative Immunofluorescence Mapping of HSP70’s Neuroprotective Effects in FUS-ALS Mouse Models
Copyright © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Final published version, 3.69 MBLicence: CC BY 4.0

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title = "Quantitative Immunofluorescence Mapping of HSP70{\textquoteright}s Neuroprotective Effects in FUS-ALS Mouse Models",

abstract = "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{\textquoteright}s impact on mitigating FUS-related pathology in ALS.",

keywords = "heat shock proteins, HSP70, HSPA1A, neurodegeneration, primary motor cortex, amyotrophic lateral sclerosis, ALS, fused in sarcoma, FUS, transgenic animals, immunofluorescence, microscopy",

author = "Piavchenko, {Gennadii A.} and Pokidova, {Ksenia S.} and Kuzmin, {Egor A.} and Venediktov, {Artem A.} and Izmailov, {Ilya Y.} and Meglinski, {Igor V.} and Kuznetsov, {Sergey L.}",

note = "Copyright {\textcopyright} 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).",

year = "2024",

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doi = "10.3390/app142411614",

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AU - Piavchenko, Gennadii A.

AU - Pokidova, Ksenia S.

AU - Kuzmin, Egor A.

AU - Venediktov, Artem A.

AU - Izmailov, Ilya Y.

AU - Meglinski, Igor V.

AU - Kuznetsov, Sergey L.

N1 - Copyright © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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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KW - ALS

KW - fused in sarcoma

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KW - transgenic animals

KW - immunofluorescence

KW - microscopy

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JF - Applied Sciences

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

Abstract

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