Aperçu : G.M.
Les
phosphoinositides sont des composants essentiels des membranes
lipidiques et des régulateurs cruciaux de nombreuses fonctions
cellulaires, notamment la transduction du signal, le trafic des
vésicules, la localisation et l'activité des récepteurs membranaires et
la détermination de l'identité de la membrane. Les
études génétiques et fonctionnelles montrent de plus en plus que ces
enzymes sont souvent dysrégulées ou mutées dans les troubles du spectre de l'autisme. [...] cela offre des possibilités intéressantes d'explorer le
métabolisme phosphoinositide altéré comme une cible thérapeutique chez
les personnes avec certaines formes d'autisme. Cette
revue résume les études génétiques et fonctionnelles qui identifient
les défauts du métabolisme des phosphoinositides dans l'autisme et les
troubles apparentés...
J Neurosci Res. 2017 May;95(5):1161-1173. doi: 10.1002/jnr.23797. Epub 2016 Jul 4.
Defective phosphoinositide metabolism in autism
Gross C1,2.
Author information
- 1
- Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
- 2
- Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
Abstract
Phosphoinositides
are essential components of lipid membranes and crucial regulators of
many cellular functions, including signal transduction, vesicle
trafficking, membrane receptor localization and activity, and
determination of membrane identity. These functions depend on the
dynamic and highly regulated metabolism of phosphoinositides and require
finely balanced activity of specific phosphoinositide kinases and
phosphatases. There is increasing evidence from genetic and functional
studies that these enzymes are often dysregulated or mutated in autism
spectrum disorders; in particular, phosphoinositide 3-kinases and their
regulatory subunits appear to be affected frequently. Examples of autism spectrum disorders with defective phosphoinositide metabolism are fragile X syndrome and autism
disorders associated with mutations in the phosphoinositide
3-phosphatase tensin homolog deleted on chromosome 10 (PTEN), but recent
genetic analyses also suggest that select nonsyndromic, idiopathic
forms of autism
may have altered activity of phosphoinositide kinases and phosphatases.
Isoform-specific inhibitors for some of the phosphoinositide kinases
have already been developed for cancer research and treatment, and a few
are being evaluated for use in humans. Altogether, this offers exciting
opportunities to explore altered phosphoinositide metabolism as a
therapeutic target in individuals with certain forms of autism. This review summarizes genetic and functional studies identifying defects in phosphoinositide metabolism in autism
and related disorders, describes published preclinical work targeting
phosphoinositide 3-kinases in neurological diseases, and discusses the
opportunities and challenges ahead to translate these findings from
animal models and human cells into clinical application in humans. ©
2016 Wiley Periodicals, Inc.
© 2016 Wiley Periodicals, Inc.
- PMID: 27376697
- PMCID: PMC5214992 [Available on 2017-11-01]
- DOI: 10.1002/jnr.23797
