miR128 up-regulation correlates with impaired amyloid β(1-42) degradation in monocytes from patients with sporadic Alzheimer's disease.
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.
Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Perugia, Perugia, Italy.
Roberto
R
Tiribuzi
Lucia
L
Crispoltoni
Serena
S
Porcellati
Martina
M
Di Lullo
Fulvio
F
Florenzano
Matteo
M
Pirro
Francesco
F
Bagaglia
Toshitaka
T
Kawarai
Mauro
M
Zampolini
Aldo
A
Orlacchio
Antonio
A
Orlacchio
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002403:Cathepsins / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D059748:Proteolysis; D015854:Up-Regulation; D043323:alpha-Mannosidase / Q000378:metabolism / Q000502:physiology; D001616:beta-Galactosidase / Q000378:metabolism / Q000502:physiology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism / Q000502:physiology
D016229:Amyloid beta-Peptides; D035683:MicroRNAs; C550324:Mirn128 microRNA, mouse; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D001616:beta-Galactosidase; D043323:alpha-Mannosidase; D001619:beta-N-Acetylhexosaminidases; D002403:Cathepsins
Cathepsin B; Lysosomal enzymes; Monocytes; Sporadic Alzheimer's disease; TFEB; miR-128