Preclinical evaluation of the PI3K/Akt/mTOR pathway in animal models of multiple sclerosis

Oncotarget
Santa MammanaKatia Mangano

Abstract

The PI3K/AKT/mTOR pathway is an intracellular signalling pathway that regulates cell activation. proliferation, metabolism and apoptosis. Increasing body of data suggests that alterations in the PI3K/AKT/mTOR pathway may result in an enhanced susceptibility to autoimmunity. Multiple Sclerosis (MS) is one of the most common chronic inflammatory diseases of the central nervous system leading to demyelination and neurodegeneration. In the current study, we have firstly evaluated in silico the involvement of the mTOR network on the generation and progression of MS and on oligodendrocyte function, making use of currently available whole-genome transcriptomic data. Then, the data generated in silico were subjected to an ex-vivo evaluation. To this aim, the involvement of mTOR was validated on a well-known animal model of MS andin vitroon Th17 cells. Our data indicate that there is a significant involvement of the mTOR network in the etiopathogenesis of MS and that Rapamycin treatment may represent a useful therapeutic approach in this clinical setting. On the other hand, our data showed that a significant involvement of the mTOR network could be observed only in the early phases of oligodendrocyte maturation, but not in the maturatio...Continue Reading

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Citations

Jul 13, 2019·International Journal of Immunopathology and Pharmacology·Katia ManganoAntonio Di Cataldo
Jul 25, 2019·Brain Sciences·Salvo Danilo LombardoMaria Cristina Petralia
Sep 5, 2019·Brain Sciences·Salvo Danilo LombardoAlessia Bramanti
Dec 22, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eugenio CavalliMaria Cristina Petralia
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Mar 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eugenio CavalliMaria Sofia Basile
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Jul 7, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maria Cristina PetraliaMaria Sofia Basile
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Nov 18, 2020·Brain Sciences·Lyubka TanchevaFerdinando Nicoletti
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Jan 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rosario CaltabianoPaolo Fagone
Aug 28, 2020·Neurochemistry International·Dia AdvaniPravir Kumar
Oct 16, 2020·Journal of Molecular Neuroscience : MN·Cristina SanfilippoMichelino Di Rosa

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Datasets Mentioned

BETA
GSE29606
GSE38645
GSE48872

Methods Mentioned

BETA
ELISA
PCR

Software Mentioned

GraphPad Prism
GEO2R
ENVIGO RMS
STRING

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