Alzheimer's disease (AD), the most common form of dementia in the elderly, is characterized by neurofibrillary tangles, extracellular amyloid plaques and neuroinflammation. New evidences have 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, -Gal, -Man and -Hex, were less expressed in monocytes and lymphocytes from patients with a clinical diagnosis of AD dementia compared to 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 amyloid β-peptide (Aβ42) degradation. These results could contribute to clarify the molecular mechanisms which affect the imbalanced amyloid production/clearance involved in the pathogenesis of Alzheimer’s disease.
MicroRNA mediated lysosomal enzymes down-regulation in cell of peripheral system from aAlzheimer's disease patients
TIRIBUZI, ROBERTO;CRISPOLTONI, LUCIA;ORLACCHIO, Aldo;ZAMPOLINI, MAURO;PORCELLATI, Serena;DATTI, Alessandro;MARTINO, Sabata;
2012
Abstract
Alzheimer's disease (AD), the most common form of dementia in the elderly, is characterized by neurofibrillary tangles, extracellular amyloid plaques and neuroinflammation. New evidences have 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, -Gal, -Man and -Hex, were less expressed in monocytes and lymphocytes from patients with a clinical diagnosis of AD dementia compared to 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 amyloid β-peptide (Aβ42) degradation. These results could contribute to clarify the molecular mechanisms which affect the imbalanced amyloid production/clearance involved in the pathogenesis of Alzheimer’s disease.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
