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.

Tiribuzi, R., Crispoltoni, L., Porcellati, S., Di Lullo, M., Florenzano, F., Pirro, M., et al. (2014). miR128 up-regulation correlates with impaired amyloid β(1-42) degradation in monocytes from patients with sporadic Alzheimer's disease. NEUROBIOLOGY OF AGING, 35(2), 345-356 [10.1016/j.neurobiolaging.2013.08.003].

miR128 up-regulation correlates with impaired amyloid β(1-42) degradation in monocytes from patients with sporadic Alzheimer's disease

ORLACCHIO, ANTONIO;
2014-02-01

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.
feb-2014
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - NEUROLOGIA
English
Con Impact Factor ISI
Proteolysis; beta-N-Acetylhexosaminidases; miR-128; MicroRNAs; beta-Galactosidase; Humans; Cathepsin B; Alzheimer Disease; TFEB; Aged; Lymphocytes; Cathepsins; Lysosomal enzymes; Peptide Fragments; Amyloid beta-Peptides; Cells, Cultured; Sporadic Alzheimer's disease; alpha-Mannosidase; Up-Regulation; Monocytes; Male; Lysosomes; Female
Tiribuzi, R., Crispoltoni, L., Porcellati, S., Di Lullo, M., Florenzano, F., Pirro, M., et al. (2014). miR128 up-regulation correlates with impaired amyloid β(1-42) degradation in monocytes from patients with sporadic Alzheimer's disease. NEUROBIOLOGY OF AGING, 35(2), 345-356 [10.1016/j.neurobiolaging.2013.08.003].
Tiribuzi, R; Crispoltoni, L; Porcellati, S; Di Lullo, M; Florenzano, F; Pirro, M; Bagaglia, F; Kawarai, T; Zampolini, M; Orlacchio, A; Orlacchio, A...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/99288
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