Favorably against the odds - autophagy control despite advanced amyloid- ß toxicity

Alzheimer disease (AD) is a devastating condition associated with loss of proteostasis control and autophagy failure, leading to progressive neuronal cell death. However, the relationship between the activity in macroautophagy (MA) and chaperone-mediated autophagy (CMA) in the context of cargo clear...

Full description

Bibliographic Details
Main Authors: Claudia M Ntsapi, Andre du Toit, Ben Loos
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Autophagy Reports
Subjects:
Online Access:http://dx.doi.org/10.1080/27694127.2022.2082631
_version_ 1827818549246164992
author Claudia M Ntsapi
Andre du Toit
Ben Loos
author_facet Claudia M Ntsapi
Andre du Toit
Ben Loos
author_sort Claudia M Ntsapi
collection DOAJ
description Alzheimer disease (AD) is a devastating condition associated with loss of proteostasis control and autophagy failure, leading to progressive neuronal cell death. However, the relationship between the activity in macroautophagy (MA) and chaperone-mediated autophagy (CMA) in the context of cargo clearance remains poorly dissected. We have found that cell death is observed as early as 24 h into amyloid-induced toxicity, despite enhanced and fully functional autophagy activity even at late stages of injury progression, whereas inhibition of autophagosome degradation indeed shifts apoptosis onset to an earlier point in time. A prolonged intermittent fasting (IF) regimen during severe paraquat-induced neuronal injury enhances both MA- and CMA-associated protein clearance in the brain differentially and region-specifically. These results have a number of practical implications that point towards a major focus to decrease proteinaceous cargo burden, while enhancing autophagy flux early and late in the pathogenesis, so as to rapidly offset the disequilibrium between cargo and machinery flux. In this punctum, we summarize these findings.
first_indexed 2024-03-12T00:55:22Z
format Article
id doaj.art-9f106a2a07b447a9be1caa41f0a82028
institution Directory Open Access Journal
issn 2769-4127
language English
last_indexed 2024-03-12T00:55:22Z
publishDate 2022-12-01
publisher Taylor & Francis Group
record_format Article
series Autophagy Reports
spelling doaj.art-9f106a2a07b447a9be1caa41f0a820282023-09-14T13:24:40ZengTaylor & Francis GroupAutophagy Reports2769-41272022-12-011124224610.1080/27694127.2022.20826312082631Favorably against the odds - autophagy control despite advanced amyloid- ß toxicityClaudia M Ntsapi0Andre du Toit1Ben Loos2University of the Free StateStellenbosch UniversityStellenbosch UniversityAlzheimer disease (AD) is a devastating condition associated with loss of proteostasis control and autophagy failure, leading to progressive neuronal cell death. However, the relationship between the activity in macroautophagy (MA) and chaperone-mediated autophagy (CMA) in the context of cargo clearance remains poorly dissected. We have found that cell death is observed as early as 24 h into amyloid-induced toxicity, despite enhanced and fully functional autophagy activity even at late stages of injury progression, whereas inhibition of autophagosome degradation indeed shifts apoptosis onset to an earlier point in time. A prolonged intermittent fasting (IF) regimen during severe paraquat-induced neuronal injury enhances both MA- and CMA-associated protein clearance in the brain differentially and region-specifically. These results have a number of practical implications that point towards a major focus to decrease proteinaceous cargo burden, while enhancing autophagy flux early and late in the pathogenesis, so as to rapidly offset the disequilibrium between cargo and machinery flux. In this punctum, we summarize these findings.http://dx.doi.org/10.1080/27694127.2022.2082631autophagic fluxautophagycaloric restrictionchaperone-mediated autophagymacroautophagyneuronal toxicity
spellingShingle Claudia M Ntsapi
Andre du Toit
Ben Loos
Favorably against the odds - autophagy control despite advanced amyloid- ß toxicity
Autophagy Reports
autophagic flux
autophagy
caloric restriction
chaperone-mediated autophagy
macroautophagy
neuronal toxicity
title Favorably against the odds - autophagy control despite advanced amyloid- ß toxicity
title_full Favorably against the odds - autophagy control despite advanced amyloid- ß toxicity
title_fullStr Favorably against the odds - autophagy control despite advanced amyloid- ß toxicity
title_full_unstemmed Favorably against the odds - autophagy control despite advanced amyloid- ß toxicity
title_short Favorably against the odds - autophagy control despite advanced amyloid- ß toxicity
title_sort favorably against the odds autophagy control despite advanced amyloid ss toxicity
topic autophagic flux
autophagy
caloric restriction
chaperone-mediated autophagy
macroautophagy
neuronal toxicity
url http://dx.doi.org/10.1080/27694127.2022.2082631
work_keys_str_mv AT claudiamntsapi favorablyagainsttheoddsautophagycontroldespiteadvancedamyloidßtoxicity
AT andredutoit favorablyagainsttheoddsautophagycontroldespiteadvancedamyloidßtoxicity
AT benloos favorablyagainsttheoddsautophagycontroldespiteadvancedamyloidßtoxicity