Tipping the scales: Lessons from simple model systems on inositol imbalance in neurological disorders.
Inositol and inositol-containing compounds have signalling and regulatory roles in many cellular processes, suggesting that inositol imbalance may lead to wide-ranging changes in cellular functions. Indeed, changes in inositol-dependent signalling have been implicated in various diseases and cellular functions such as autophagy, and these changes have often been proposed as therapeutic targets. However, few studies have highlighted the links between inositol depletion and the downstream effects on inositol phosphates and phosphoinositides in disease states. For this research, many advances have employed simple model systems that include the social amoeba D. discoideum and the yeast S. cerevisiae, since these models enable a range of experimental approaches that are not possible in mammalian models. In this review, we discuss recent findings initiated in simple model systems and translated to higher model organisms where the effect of altered inositol, inositol phosphate and phosphoinositide levels impact on bipolar disorder, Alzheimer disease, epilepsy and autophagy.
Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham TW20 OEX, United Kingdom.
Anna D
AD
Frej
Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham TW20 OEX, United Kingdom.
Grant P
GP
Otto
Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham TW20 OEX, United Kingdom. Electronic address: robin.williams@rhul.ac.uk.
Robin S B
RS
Williams
D000818:Animals; D001343:Autophagy / Q000502:physiology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D009422:Nervous System Diseases / Q000378:metabolism* / Q000473:pathology; D010716:Phosphatidylinositols / Q000378:metabolism*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols
Alzheimer disease; Autophagy; Bipolar disorder; Dictyostelium discoideum; Epilepsy; INO1; Inositol