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miR128 up-regulation correlates with impaired amyloid β(1-42) degradation in monocytes from patients with sporadic Alzheimer's disease.
- Source :
-
Neurobiology of aging [Neurobiol Aging] 2014 Feb; Vol. 35 (2), pp. 345-56. Date of Electronic Publication: 2013 Sep 21. - Publication Year :
- 2014
-
Abstract
- Alzheimer's disease (AD), the most common form of dementia in elderly individuals, is characterized by neurofibrillary tangles, extracellular amyloid-β (Aβ) plaques and neuroinflammation. New evidence has shown that the lysosomal system might be a crossroad in which etiological factors in AD pathogenesis converge. This study shows that several lysosomal enzymes, including Cathepsin B, D, S, β-Galactosidase, α-Mannosidase, and β-Hexosaminidase, were less expressed in monocytes and lymphocytes from patients with a clinical diagnosis of AD dementia compared with cells from healthy controls. In vitro experiments of gain and loss of function suggest that down-regulation is a direct consequence of miR-128 up-regulation found in AD-related cells. The present study also demonstrates that miR-128 inhibition in monocytes from AD patients improves Aβ(1-42) degradation. These results could contribute to clarify the molecular mechanisms that affect the imbalanced Aβ production/clearance involved in the pathogenesis of AD.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Aged
Cathepsins metabolism
Cathepsins physiology
Cells, Cultured
Female
Humans
Lymphocytes enzymology
Lymphocytes metabolism
Lysosomes enzymology
Male
Monocytes enzymology
Up-Regulation
alpha-Mannosidase metabolism
alpha-Mannosidase physiology
beta-Galactosidase metabolism
beta-Galactosidase physiology
beta-N-Acetylhexosaminidases metabolism
beta-N-Acetylhexosaminidases physiology
Alzheimer Disease genetics
Alzheimer Disease metabolism
Amyloid beta-Peptides metabolism
MicroRNAs metabolism
Monocytes metabolism
Peptide Fragments metabolism
Proteolysis
Subjects
Details
- Language :
- English
- ISSN :
- 1558-1497
- Volume :
- 35
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neurobiology of aging
- Publication Type :
- Academic Journal
- Accession number :
- 24064186
- Full Text :
- https://doi.org/10.1016/j.neurobiolaging.2013.08.003