Overexpression of RAC2 in Alzheimer's disease brains increased microglia phagocytosis

Libei Zhu

doi:10.54097/yk6y5n95

Authors

Libei Zhu

DOI:

https://doi.org/10.54097/yk6y5n95

Keywords:

Alzheimer's disease, microglia, phagocytosis, RAC2.

Abstract

Alzheimer's disease (AD) is a degenerative neurological disease characterized by memory impairment, agnosia, and loss of motor function. Although treatment is available to alleviate symptoms, there is no cure due to limited understanding of its pathogenesis. Amyloid protein amyloid-β (Aβ) is believed to be the core mechanism of disease onset. And several studies reported that Aβ plaque could be effectively cleared by microglia, thereby preventing AD progression. Yet as a double-edged sword, microglia over-activation would cause unexpected neuroinflammation in patients with AD. To understand the dysfunction of microglia in AD, single-cell RNA-sequencing (scRNA-seq) was used to precisely determine the gene expression of microglia populations. Several genes involved phagocytosis showed decreased expression in microglia of AD brains. The upregulated RAC2, a small Rho-GTPase (GTP enzyme), was selected to explore its function in microglia activation. Results from in vitro experiments further revealed the up-regulation of RAC2 in microglia of AD patient may mediate the microglia phagocytosis to Aβ. Therefore, the up-regulation of RAC2 can potentially reduce the level of Aβ protein in AD patients and delay the progression of the disease. We hope that the results of the experiment will provide more helpful information for the treatment of AD.

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