Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive performance. Recent genetic work has revealed a prominent role of innate immunity in the disease. The immune system of the brain is constituted by microglia, which derive from primitive macrophages of the yolk sac and have essential functions in the development, maintenance and protection of this organ. These cells are also responsible of neuroinflammation through the production and release of different cytokines and other pro-inflammatory molecules. The control of the HIF/PHD pathway over innate immune cells has been studied in the last years. In particular, prolyl-hydroxilase 3 (PHD3) expression identifies pro-inflammatory macrophages both in vivo and in vitro and the role of PHD3 in sepsis and immune-mediated inflammatory diseases is being described. However, there is little knowledge about the contribution of PHDs to microglia function and the consequences of the alteration of the HIF/PHD pathway in the pathology of AD. In particular, here we focus in AD models that present accumulated HIF1¿ in the brain and a strong expression of PHD3 in microglial cells. We show histological, biochemical and behavioral data of AD mice in the absence of PHD3 and discuss the implications in the progression of AD and their possible therapeutic implications.

Póster presentado en Hypoxia: From Basic Mechanisms to Therapeutics, celebrado en Dublín del 12 al 15 de mayo de 2015.

Peer Reviewed