期刊
NEUROBIOLOGY OF AGING
卷 35, 期 2, 页码 345-356出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2013.08.003
关键词
Sporadic Alzheimer's disease; Lysosomal enzymes; Cathepsin B; miR-128; TFEB; Monocytes
资金
- Italian Ministry of Health [RF-UMB-2006-339457, GR09.109]
- Italian Ministry of Education, University, and Research [2010KL2Y73_002]
- Comitato Telethon Fondazione Onlus, Italy [GGP10121]
Alzheimer's disease (AD), the most common form of dementia in elderly individuals, is characterized by neurofibrillary tangles, extracellular amyloid-beta (A beta) 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, beta-Galactosidase, alpha-Mannosidase, and beta-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 A beta(1-42) degradation. These results could contribute to clarify the molecular mechanisms that affect the imbalanced A beta production/clearance involved in the pathogenesis of AD. (C) 2014 Elsevier Inc. All rights reserved.
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