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Lysosomal Enzyme Glucocerebrosidase Protects against Aβ(1-42) Oligomer-Induced Neurotoxicity
Glucocerebrosidase (GCase) functions as a lysosomal enzyme and its mutations are known to be related to many neurodegenerative diseases, including Gaucher’s disease (GD), Parkinson’s disease (PD), and Dementia with Lewy Bodies (DLB). However, there is little information about the role of GCase in th...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668030/ https://www.ncbi.nlm.nih.gov/pubmed/26629917 http://dx.doi.org/10.1371/journal.pone.0143854 |
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author | Choi, Seulah Kim, Donghoon Kam, Tae-In Yun, Seungpil Kim, Sangjune Park, Hyejin Hwang, Heehong Pletnikova, Olga Troncoso, Juan C. Dawson, Valina L. Dawson, Ted M. Ko, Han Seok |
author_facet | Choi, Seulah Kim, Donghoon Kam, Tae-In Yun, Seungpil Kim, Sangjune Park, Hyejin Hwang, Heehong Pletnikova, Olga Troncoso, Juan C. Dawson, Valina L. Dawson, Ted M. Ko, Han Seok |
author_sort | Choi, Seulah |
collection | PubMed |
description | Glucocerebrosidase (GCase) functions as a lysosomal enzyme and its mutations are known to be related to many neurodegenerative diseases, including Gaucher’s disease (GD), Parkinson’s disease (PD), and Dementia with Lewy Bodies (DLB). However, there is little information about the role of GCase in the pathogenesis of Alzheimer’s disease (AD). Here we demonstrate that GCase protein levels and enzyme activity are significantly decreased in sporadic AD. Moreover, Aβ(1–42) oligomer treatment results in neuronal cell death that is concomitant with decreased GCase protein levels and enzyme activity, as well as impairment in lysosomal biogenesis and acidification. Importantly, overexpression of GCase promotes the lysosomal degradation of Aβ(1–42) oligomers, restores the lysosomal impairment, and protects against the toxicity in neurons treated with Aβ(1–42) oligomers. Our findings indicate that a deficiency of GCase could be involved in progression of AD pathology and suggest that augmentation of GCase activity may be a potential therapeutic option for the treatment of AD. |
format | Online Article Text |
id | pubmed-4668030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46680302015-12-10 Lysosomal Enzyme Glucocerebrosidase Protects against Aβ(1-42) Oligomer-Induced Neurotoxicity Choi, Seulah Kim, Donghoon Kam, Tae-In Yun, Seungpil Kim, Sangjune Park, Hyejin Hwang, Heehong Pletnikova, Olga Troncoso, Juan C. Dawson, Valina L. Dawson, Ted M. Ko, Han Seok PLoS One Research Article Glucocerebrosidase (GCase) functions as a lysosomal enzyme and its mutations are known to be related to many neurodegenerative diseases, including Gaucher’s disease (GD), Parkinson’s disease (PD), and Dementia with Lewy Bodies (DLB). However, there is little information about the role of GCase in the pathogenesis of Alzheimer’s disease (AD). Here we demonstrate that GCase protein levels and enzyme activity are significantly decreased in sporadic AD. Moreover, Aβ(1–42) oligomer treatment results in neuronal cell death that is concomitant with decreased GCase protein levels and enzyme activity, as well as impairment in lysosomal biogenesis and acidification. Importantly, overexpression of GCase promotes the lysosomal degradation of Aβ(1–42) oligomers, restores the lysosomal impairment, and protects against the toxicity in neurons treated with Aβ(1–42) oligomers. Our findings indicate that a deficiency of GCase could be involved in progression of AD pathology and suggest that augmentation of GCase activity may be a potential therapeutic option for the treatment of AD. Public Library of Science 2015-12-02 /pmc/articles/PMC4668030/ /pubmed/26629917 http://dx.doi.org/10.1371/journal.pone.0143854 Text en © 2015 Choi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Choi, Seulah Kim, Donghoon Kam, Tae-In Yun, Seungpil Kim, Sangjune Park, Hyejin Hwang, Heehong Pletnikova, Olga Troncoso, Juan C. Dawson, Valina L. Dawson, Ted M. Ko, Han Seok Lysosomal Enzyme Glucocerebrosidase Protects against Aβ(1-42) Oligomer-Induced Neurotoxicity |
title | Lysosomal Enzyme Glucocerebrosidase Protects against Aβ(1-42) Oligomer-Induced Neurotoxicity |
title_full | Lysosomal Enzyme Glucocerebrosidase Protects against Aβ(1-42) Oligomer-Induced Neurotoxicity |
title_fullStr | Lysosomal Enzyme Glucocerebrosidase Protects against Aβ(1-42) Oligomer-Induced Neurotoxicity |
title_full_unstemmed | Lysosomal Enzyme Glucocerebrosidase Protects against Aβ(1-42) Oligomer-Induced Neurotoxicity |
title_short | Lysosomal Enzyme Glucocerebrosidase Protects against Aβ(1-42) Oligomer-Induced Neurotoxicity |
title_sort | lysosomal enzyme glucocerebrosidase protects against aβ(1-42) oligomer-induced neurotoxicity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668030/ https://www.ncbi.nlm.nih.gov/pubmed/26629917 http://dx.doi.org/10.1371/journal.pone.0143854 |
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