The Decrease of Uch-L1 Activity Is a Common Mechanism Responsible for Aβ 42 Accumulation in Alzheimer's and Vascular Disease.

Details

Ressource 1Download: 29033830_BIB_65E7F614BD5F.pdf (1867.10 [Ko])
State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_65E7F614BD5F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Decrease of Uch-L1 Activity Is a Common Mechanism Responsible for Aβ 42 Accumulation in Alzheimer's and Vascular Disease.
Journal
Frontiers in aging neuroscience
Author(s)
Guglielmotto M., Monteleone D., Vasciaveo V., Repetto I.E., Manassero G., Tabaton M., Tamagno E.
ISSN
1663-4365 (Print)
ISSN-L
1663-4365
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
9
Pages
320
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Alzheimer's disease (AD) is a multifactorial pathology causing common brain spectrum disorders in affected patients. These mixed neurological disorders not only include structural AD brain changes but also cerebrovascular lesions. The main aim of the present issue is to find the factors shared by the two pathologies. The decrease of ubiquitin C-terminal hydrolase L1 (Uch-L1), a major neuronal enzyme involved in the elimination of misfolded proteins, was observed in ischemic injury as well as in AD, but its role in the pathogenesis of AD is far to be clear. In this study we demonstrated that Uch-L1 inhibition induces BACE1 up-regulation and increases neuronal and apoptotic cell death in control as well as in transgenic AD mouse model subjected to Bengal Rose, a light-sensitive dye inducing that induces a cortical infarction through photo-activation. Under the same conditions we also found a significant activation of NF-κB. Thus, the restoration of Uch-L1 was able to completely prevent both the increase in BACE1 protein levels and the amount of cell death. Our data suggest that the Uch-L1-mediated BACE1 up-regulation could be an important mechanism responsible for Aβ peptides accumulation in vascular injury and indicate that the modulation of the activity of this enzyme could provide new therapeutic strategies in AD.

Keywords
Alzheimer’s disease, BACE1, Uch-L1, amyloid beta, mixed dementia
Pubmed
Web of science
Open Access
Yes
Create date
26/10/2017 9:23
Last modification date
20/08/2019 14:21
Usage data