Proliferating Microglia Exhibit Unique Transcriptional and Functional Alterations in Alzheimer's Disease.

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Tác giả: Marc Beyer, Khushbu Bhalla, Sergio Gomez-Castro, Kristian Händler, Michael T Heneka, Paula Martorell, Róisín McManus, Heela Sarlus, Eran Segal, Ilya Slutzkin, Thomas Ulas, Carmen Venegas, Ana Vieira-Saecker, Nàdia Villacampa

Ngôn ngữ: eng

Ký hiệu phân loại: 553.453 Tin

Thông tin xuất bản: United States : ASN neuro , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 750214

Proliferation of microglia represents a physiological process, which is accelerated in several neurodegenerative disorders including Alzheimer disease (AD). The effect of such neurodegeneration-associated microglial proliferation on function and disease progression remains unclear. Here, we show that proliferation results in profound alterations of cellular function by providing evidence that newly proliferated microglia show impaired beta-amyloid clearance in vivo. Through sorting of proliferating microglia of APP/PS1 mice and subsequent transcriptome analysis, we define unique proliferation-associated transcriptomic signatures that change with age and beta-amyloid accumulation and are characterized by enrichment of immune system-related pathways. Of note, we identify the DEAD-Box Helicase 3 X-Linked (DDX3X) as a key molecule to modulate microglia activation and cytokine secretion and it is expressed in the AD brain. Together, these results argue for a novel concept by which phenotypic and functional microglial changes occur longitudinally as a response to accelerated proliferation in a neurodegenerative environment.
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