Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 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 G...
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2015-01-01
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doaj-51fa112d70ee463591d8203cbdcdd3442020-11-25T01:46:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014385410.1371/journal.pone.0143854Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity.Seulah ChoiDonghoon KimTae-In KamSeungpil YunSangjune KimHyejin ParkHeehong HwangOlga PletnikovaJuan C TroncosoValina L DawsonTed M DawsonHan Seok KoGlucocerebrosidase (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, Aβ1-42 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 Aβ1-42 oligomers, restores the lysosomal impairment, and protects against the toxicity in neurons treated with Aβ1-42 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.http://europepmc.org/articles/PMC4668030?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Seulah Choi Donghoon Kim Tae-In Kam Seungpil Yun Sangjune Kim Hyejin Park Heehong Hwang Olga Pletnikova Juan C Troncoso Valina L Dawson Ted M Dawson Han Seok Ko |
spellingShingle |
Seulah Choi Donghoon Kim Tae-In Kam Seungpil Yun Sangjune Kim Hyejin Park Heehong Hwang Olga Pletnikova Juan C Troncoso Valina L Dawson Ted M Dawson Han Seok Ko Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity. PLoS ONE |
author_facet |
Seulah Choi Donghoon Kim Tae-In Kam Seungpil Yun Sangjune Kim Hyejin Park Heehong Hwang Olga Pletnikova Juan C Troncoso Valina L Dawson Ted M Dawson Han Seok Ko |
author_sort |
Seulah Choi |
title |
Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity. |
title_short |
Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity. |
title_full |
Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity. |
title_fullStr |
Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity. |
title_full_unstemmed |
Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity. |
title_sort |
lysosomal enzyme glucocerebrosidase protects against aβ1-42 oligomer-induced neurotoxicity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
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, Aβ1-42 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 Aβ1-42 oligomers, restores the lysosomal impairment, and protects against the toxicity in neurons treated with Aβ1-42 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. |
url |
http://europepmc.org/articles/PMC4668030?pdf=render |
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