Dysregulation of Phosphoinositide 5-Phosphatases and Phosphoinositides in Alzheimer's Disease

• Published in: Frontiers in neuroscience Vol. 15; p. 614855
• Main Authors: Ando, Kunie, Erneux, Christophe, Homa, Mégane, Houben, Sarah, de Fisenne, Marie-Ange, Brion, Jean-Pierre, Leroy, Karelle
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 25-02-2021; Frontiers Media S.A
• Subjects: Alzheimer's disease; Animal models; Biomarkers; Breast cancer; Cognitive ability; Diabetes mellitus; DNA methylation; Inositol polyphosphate 5-phosphatase; Inositol-1,4,5-trisphosphate 5-phosphatase; Kinases; Leukocytes; Localization; Metastases; microglia; mRNA; Neurodegenerative diseases; Neuroscience; Phagocytosis; Phosphatidylinositol 3,4,5-triphosphate; phosphoinositide phosphatases; Phosphoinositides; Phosphorylation; Plasma membranes; Post-translation; SHIP2; synaptojanin; Tau protein; Therapeutic applications; Transgenic mice; Tyrosine; phosphoinositide phosphatases; synaptojanin; SHIP2; Alzheimer's disease; microglia; phosphoinositides
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2021.614855

[...]long-time follow-up of the participants would be necessary to decipher the correlation between the level of INPP5D mRNA and cognitive decline. Since SHIP1 converts PI(3,4,5)P3 to PI(3,4)P2, the amounts of these PIs in the blood leucocytes may also be altered and needs to be further investigated (as discussed in section PI Metabolism and Autophagic-Endosomal-Lysosomal Abnormalities). [...]tau phosphorylation by GSK3ß is increased by Aß via FcγRIIb-SHIP2 complex (Kam et al., 2016). SHIP2 inhibition has been reported to partially rescue memory deficits in transgenic mouse models of diabetes and AD (Soeda et al., 2010; Kam et al., 2016) and to prevent metastasis in breast cancer cells (Ghosh et al., 2018). Since both SHIP1 and SHIP2 play critical roles in antagonizing microglial proliferation and phagocytosis, the use of both SHIP1 and SHIP2 inhibitors has been proposed in AD to enhance basal microglial homeostatic functions for therapeutic purposes (Pedicone et al., 2020). Given that SHIP2 is translocated to plasma membranes upon Aß-FcγRIIb interaction (Kam et al., 2016), subcellular localization of SHIP2 should be significantly altered in AD brains. Since FcγRIIb activation leads to tyrosine phosphorylation of SHIP2 (Muraille et al., 1999), the post-translational modifications of SHIP2 could be altered in the affected areas of AD brains.