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

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• 作者：Roberto Tiribuzi ; Lucia Crispoltoni ; Serena Porcellati ; Martina Di Lullo ; Fulvio Florenzano ; Matteo Pirro ; Francesco Bagaglia ; Toshitaka Kawarai ; Mauro Zampolini ; Aldo Orlacchio ; Antonio Orlacchio
• 关键词：Sporadic Alzheimer's disease ; Lysosomal enzymes ; Cathepsin B ; miR-128 ; TFEB ; Monocytes
• 刊名：Neurobiology of Aging
• 出版年：February, 2014
• 年：2014
• 卷：35
• 期：2
• 页码：345-356
• 全文大小：2097 K

文摘

Alzheimer's disease (AD), the most common form of dementia in elderly individuals, is characterized by neurofibrillary tangles, extracellular amyloid-尾 (A尾) 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, 尾-Galactosidase, 伪-Mannosidase, and 尾-Hexosaminidase, were less expressed in monocytes and lymphocytes from patients with a clinical diagnosis of AD dementia compared with cells from healthy controls. In聽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尾(1-42) degradation. These results could contribute to clarify the molecular mechanisms that affect the imbalanced A尾 production/clearance involved in the pathogenesis of AD.