Reaction to Endoplasmic Reticulum Stress via ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With Aging
Amyotrophic lateral sclerosis (ALS) is a multisystemic neurodegenerative disorder. Given that peripheral blood mononuclear cells (PBMCs) serve as a “window to the central nervous system” we aimed to answer whether endoplasmic reticulum (ER) stress in ALS-PBMCs is related to disease aggressiveness. W...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2019.00005/full |
| _version_ | 1818036392195784704 |
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| author | Tino Prell Tino Prell Beatrice Stubendorff Thanh Tu Le Nayana Gaur Vedrana Tadić Annekathrin Rödiger Otto W. Witte Otto W. Witte Julian Grosskreutz Julian Grosskreutz |
| author_facet | Tino Prell Tino Prell Beatrice Stubendorff Thanh Tu Le Nayana Gaur Vedrana Tadić Annekathrin Rödiger Otto W. Witte Otto W. Witte Julian Grosskreutz Julian Grosskreutz |
| author_sort | Tino Prell |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a multisystemic neurodegenerative disorder. Given that peripheral blood mononuclear cells (PBMCs) serve as a “window to the central nervous system” we aimed to answer whether endoplasmic reticulum (ER) stress in ALS-PBMCs is related to disease aggressiveness. We studied ER stress in the PBMCs of 49 patients with ALS and 31 age- and sex-matched healthy controls. The expression of a main ER stress marker, activating transcription factor 6 (ATF6), was significantly higher in ALS compared to controls, but did not correlate with age, disease severity, disease duration and disease progression rate. When ATF6 expression levels were plotted against relative D50 (rD50)-derived disease phases derived from the D50 ALS model, two distinct clusters of patients were observed: cluster 1, with progressively increasing ATF6 expression levels and cluster 2, which demonstrated stable ATF6 expression over the disease course. Individuals in the two clusters did not significantly differ in terms of ALS Functional Rating Scale-Revised (ALSFRS-R), disease aggressiveness, disease duration and subtype. However, patients with the increasing ATF6 level were significantly younger, indicating that aging processes might be related to ER stress in ALS. Our data suggest that the reaction to ER stress during disease course may be compromised in older patients with ALS. |
| first_indexed | 2024-12-10T07:10:13Z |
| format | Article |
| id | doaj.art-c721835109544b72bdd088024f443d14 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-10T07:10:13Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-c721835109544b72bdd088024f443d142022-12-22T01:58:05ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652019-01-011110.3389/fnagi.2019.00005425716Reaction to Endoplasmic Reticulum Stress via ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With AgingTino Prell0Tino Prell1Beatrice Stubendorff2Thanh Tu Le3Nayana Gaur4Vedrana Tadić5Annekathrin Rödiger6Otto W. Witte7Otto W. Witte8Julian Grosskreutz9Julian Grosskreutz10Hans Berger Department of Neurology, Jena University Hospital, Jena, GermanyCenter for Healthy Aging, Jena University Hospital, Jena, GermanyHans Berger Department of Neurology, Jena University Hospital, Jena, GermanyHans Berger Department of Neurology, Jena University Hospital, Jena, GermanyHans Berger Department of Neurology, Jena University Hospital, Jena, GermanyHans Berger Department of Neurology, Jena University Hospital, Jena, GermanyHans Berger Department of Neurology, Jena University Hospital, Jena, GermanyHans Berger Department of Neurology, Jena University Hospital, Jena, GermanyCenter for Healthy Aging, Jena University Hospital, Jena, GermanyHans Berger Department of Neurology, Jena University Hospital, Jena, GermanyCenter for Healthy Aging, Jena University Hospital, Jena, GermanyAmyotrophic lateral sclerosis (ALS) is a multisystemic neurodegenerative disorder. Given that peripheral blood mononuclear cells (PBMCs) serve as a “window to the central nervous system” we aimed to answer whether endoplasmic reticulum (ER) stress in ALS-PBMCs is related to disease aggressiveness. We studied ER stress in the PBMCs of 49 patients with ALS and 31 age- and sex-matched healthy controls. The expression of a main ER stress marker, activating transcription factor 6 (ATF6), was significantly higher in ALS compared to controls, but did not correlate with age, disease severity, disease duration and disease progression rate. When ATF6 expression levels were plotted against relative D50 (rD50)-derived disease phases derived from the D50 ALS model, two distinct clusters of patients were observed: cluster 1, with progressively increasing ATF6 expression levels and cluster 2, which demonstrated stable ATF6 expression over the disease course. Individuals in the two clusters did not significantly differ in terms of ALS Functional Rating Scale-Revised (ALSFRS-R), disease aggressiveness, disease duration and subtype. However, patients with the increasing ATF6 level were significantly younger, indicating that aging processes might be related to ER stress in ALS. Our data suggest that the reaction to ER stress during disease course may be compromised in older patients with ALS.https://www.frontiersin.org/article/10.3389/fnagi.2019.00005/fullendoplasmic reticulum stressactivating transcription factor 6unfolded protein responseperipheral blood mononuclear cellsagingprogression |
| spellingShingle | Tino Prell Tino Prell Beatrice Stubendorff Thanh Tu Le Nayana Gaur Vedrana Tadić Annekathrin Rödiger Otto W. Witte Otto W. Witte Julian Grosskreutz Julian Grosskreutz Reaction to Endoplasmic Reticulum Stress via ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With Aging Frontiers in Aging Neuroscience endoplasmic reticulum stress activating transcription factor 6 unfolded protein response peripheral blood mononuclear cells aging progression |
| title | Reaction to Endoplasmic Reticulum Stress via ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With Aging |
| title_full | Reaction to Endoplasmic Reticulum Stress via ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With Aging |
| title_fullStr | Reaction to Endoplasmic Reticulum Stress via ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With Aging |
| title_full_unstemmed | Reaction to Endoplasmic Reticulum Stress via ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With Aging |
| title_short | Reaction to Endoplasmic Reticulum Stress via ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With Aging |
| title_sort | reaction to endoplasmic reticulum stress via atf6 in amyotrophic lateral sclerosis deteriorates with aging |
| topic | endoplasmic reticulum stress activating transcription factor 6 unfolded protein response peripheral blood mononuclear cells aging progression |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2019.00005/full |
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