DNAJB6b is Downregulated in Synucleinopathies
Folke, Jonas ; Arkan, Sertan LU ; Martinsson, Isak LU ; Aznar, Susana ; Gouras, Gunnar LU
; Brudek, Tomasz
and Hansen, Christian
LU
(2021)
In Journal of Parkinson's Disease
11(4).
p.1791-1803
- Abstract
BACKGROUND: α-synuclein (α-syn) aggregation contributes to the progression of multiple neurodegenerative diseases. We recently found that the isoform b of the co-chaperone DNAJB6 is a strong suppressor of a-syn aggregation in vivo and in vitro. However, nothing is known about the role of the endogenous isoform b of DNAJB6 (DNAJB6b) in health and disease, due to lack of specific antibodies.
OBJECTIVE: Here we generated a novel anti-DNAJB6b antibody to analyze the localization and expression this isoform in cells, in tissue and in clinical material.
METHODS: To address this we used immunocytochemistry, immunohistochemistry, as well as a novel quantitative DNAJB6 specific ELISA method.
RESULTS: The endogenous protein is... (More)
BACKGROUND: α-synuclein (α-syn) aggregation contributes to the progression of multiple neurodegenerative diseases. We recently found that the isoform b of the co-chaperone DNAJB6 is a strong suppressor of a-syn aggregation in vivo and in vitro. However, nothing is known about the role of the endogenous isoform b of DNAJB6 (DNAJB6b) in health and disease, due to lack of specific antibodies.
OBJECTIVE: Here we generated a novel anti-DNAJB6b antibody to analyze the localization and expression this isoform in cells, in tissue and in clinical material.
METHODS: To address this we used immunocytochemistry, immunohistochemistry, as well as a novel quantitative DNAJB6 specific ELISA method.
RESULTS: The endogenous protein is mainly expressed in the cytoplasm and in neurites in vitro, where it is found more in dendrites than in axons. We further verified in vivo that DNAJB6b is expressed in the dopaminergic neurons of the substantia nigra pars compacta (SNpc), which is a neuronal subpopulation highly sensitive to α-syn aggregation, that degenerate to a large extend in patients with Parkinson's disease (PD) and multiple system atrophy (MSA). When we analyzed the expression levels of DNAJB6b in brain material from PD and MSA patients, we found a downregulation of DNAJB6b by use of ELISA based quantification. Interestingly, this was also true when analyzing tissue from patients with progressive supranuclear palsy, a taupathic atypical parkinsonian disorder. However, the total level of DNAJB6 was upregulated in these three diseases, which may indicate an upregulation of the other major isoform of DNAJB6, DNAJB6a.
CONCLUSION: This study shows that DNAJB6b is downregulated in several different neurodegenerative diseases, which makes it an interesting target to further investigate in relation to amyloid protein aggregation and disease progression.
(Less)
- author
- Folke, Jonas
; Arkan, Sertan
LU
; Martinsson, Isak
LU
; Aznar, Susana
; Gouras, Gunnar
LU
; Brudek, Tomasz
and Hansen, Christian
LU
- organization
- publishing date
- 2021-07-26
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Parkinson's Disease
- volume
- 11
- issue
- 4
- pages
- 13 pages
- publisher
- IOS Press
- external identifiers
-
- pmid:34334418
- scopus:85117386576
- ISSN
- 1877-718X
- DOI
- 10.3233/JPD-202512
- language
- English
- LU publication?
- yes
- id
- fff24ba7-a7d8-4826-a784-f2a363bb0a7a
- date added to LUP
- 2021-09-06 11:17:15
- date last changed
- 2024-06-15 15:48:50
@article{fff24ba7-a7d8-4826-a784-f2a363bb0a7a,
abstract = {{<p>BACKGROUND: α-synuclein (α-syn) aggregation contributes to the progression of multiple neurodegenerative diseases. We recently found that the isoform b of the co-chaperone DNAJB6 is a strong suppressor of a-syn aggregation in vivo and in vitro. However, nothing is known about the role of the endogenous isoform b of DNAJB6 (DNAJB6b) in health and disease, due to lack of specific antibodies.</p><p>OBJECTIVE: Here we generated a novel anti-DNAJB6b antibody to analyze the localization and expression this isoform in cells, in tissue and in clinical material.</p><p>METHODS: To address this we used immunocytochemistry, immunohistochemistry, as well as a novel quantitative DNAJB6 specific ELISA method.</p><p>RESULTS: The endogenous protein is mainly expressed in the cytoplasm and in neurites in vitro, where it is found more in dendrites than in axons. We further verified in vivo that DNAJB6b is expressed in the dopaminergic neurons of the substantia nigra pars compacta (SNpc), which is a neuronal subpopulation highly sensitive to α-syn aggregation, that degenerate to a large extend in patients with Parkinson's disease (PD) and multiple system atrophy (MSA). When we analyzed the expression levels of DNAJB6b in brain material from PD and MSA patients, we found a downregulation of DNAJB6b by use of ELISA based quantification. Interestingly, this was also true when analyzing tissue from patients with progressive supranuclear palsy, a taupathic atypical parkinsonian disorder. However, the total level of DNAJB6 was upregulated in these three diseases, which may indicate an upregulation of the other major isoform of DNAJB6, DNAJB6a.</p><p>CONCLUSION: This study shows that DNAJB6b is downregulated in several different neurodegenerative diseases, which makes it an interesting target to further investigate in relation to amyloid protein aggregation and disease progression.</p>}},
author = {{Folke, Jonas and Arkan, Sertan and Martinsson, Isak and Aznar, Susana and Gouras, Gunnar and Brudek, Tomasz and Hansen, Christian}},
issn = {{1877-718X}},
language = {{eng}},
month = {{07}},
number = {{4}},
pages = {{1791--1803}},
publisher = {{IOS Press}},
series = {{Journal of Parkinson's Disease}},
title = {{DNAJB6b is Downregulated in Synucleinopathies}},
url = {{http://dx.doi.org/10.3233/JPD-202512}},
doi = {{10.3233/JPD-202512}},
volume = {{11}},
year = {{2021}},
}