fig1

Figure 1. Illustration of the proposed favorable effect of CXCR4/CXCL12 inhibition by AMD3100. (A) Bone marrow: HSCs, colored green, with CXCR4, colored red, are anchored to bone marrow stromal cells by the chemokine CXCL12, colored yellow. Administration of the CXCR4 antagonist (AMD3100), colored cyan, leads to the breakdown of the CXCR4/CXCL12 complex and the release of CXCL12 and HSCs from the stromal cells into the bloodstream; (B) Blood vessels: HSCs from the blood are recruited into the injured brain; (C) CNS: The HSCs undergo possible trans-differentiation into microglia-like cells, colored light blue, that contribute to increased cognition, increased anti-inflammatory cytokines, and reduced TAU and APP pathologies in AD. Astrocytes, colored white-orange, are present inside the brain and contribute to the reduced Glutamate toxicity in AD and to the remyelination of the damaged neurons. The astrocyte-microglia interaction is involved in CXCR4-dependent glutamate release and activated microglia amplify glutamate release from astrocytes. Created with The GIMP team, GIMP 2.8.10, www.gimp.org, 1997-2014, retrieved on 31.07.2014. HSCs: Hematopoietic stem cells; CXCR4: chemokine receptor type 4; CNS: central nervous system; APP: amyloid precursor protein; AD: Alzheimer’s disease; Ils: interleukins, TNFα: tumor necrosis factor-alpha.