Eugenio Barone (Italy)
Sapienza University of Rome
Dept. of Biochemical Sciences
Eugenio Barone graduated in Pharmaceutical Chemistry and Technology in 2006 and got a PhD in Neuroscience in 2011. The overarching goal of his laboratory is to clarify the link between defects of neurotrophic signaling (insulin and GLP1) and increased cell damage during aging and neurodegeneration. Prof. Barone authored 84 publications, most of which deal with the role of oxidative stress and insulin resistance in neurodegenerative disorders, i.e., Alzheimer's disease and Down syndrome. He is currently a member of several international societies including T21RS, SFRBM, EASD, and ISN. Prof. Barone has been co-chair of the Society for Free Radical Biology and Medicine (SFRBM) External Marketing/PR Committee (2016-2019). Currently, he is SFRBM Council Member and Chair of the SFRBM Junior Award Committee as well as Chair for the T21RS Membership and Sponsorship Committee. In 2021 he was appointed as co-chair for the European Brain Research Area (EBRA) for the Trisomy 21 cluster. He was the recipient of prestigious grants from the Alzheimer Association (2020-23), Jerome Lejeune Foundation (2019-21), European Commission (2014-16), and Italian Ministry of Research (2015-18), among the others. Finally, Prof. Barone was the recipient of several international awards including those from SFRBM (2015 and 2016), EPHAR (2013), AAIC (2017) and T21RS (2017).

Presenter of 1 Presentation

 Conference Calendar

ABERRANT CROSSTALK BETWEEN INSULIN SIGNALING AND MTOR IN YOUNG DOWN SYNDROME INDIVIDUALS REVEALED BY NEURONAL-DERIVED EXTRACELLULAR VESICLES

Session Name
1100 - RISK PATHWAYS, INSULIN, PSYCHOSOCIAL AND PSYCHIATRIC SYMPTOMS IN NEURODEGENERATIVE DISEASES (ID 217)
Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
09:10 AM - 11:10 AM
Room
ONSITE: 133-134
Lecture Time
09:40 AM - 09:55 AM
Presenter

Abstract

Aims

Intellectual disability, accelerated aging and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). While growing research aims at the identification of molecular pathways underlying the aging trajectory of DS population data on infants and adolescents with DS are missing.

Methods

Plasma-resident neuronal-derived extracellular vesicles (nEVs) were isolated form healthy donors (HD, n=17) and DS children (n=18) aging from 2 to 17 years who underwent complete clinical workup and routine biochemistry. nEVs were first characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM) and probed for nEVs markers (L1CAM, CD81, Alix and APOA1). Afterwards, nEVs content was interrogated for markers of insulin/mTOR pathways as well as for proteins involved in synaptic plasticity, i.e., sintaxin-1, PSD95 and pCamKIIα-Thr286.

Results

nEVs isolated from DS children were characterized by a significant increase of pIRS1Ser636, a marker of insulin resistance, and the hyperactivation of the Akt/mTOR/p70S6K axis downstream from IRS1, likely driven by the higher inhibition of PTEN. High levels of pGSK3bSer9 were also found. These alterations occur independent of peripheral alterations. Interestingly, the activation of both Akt and mTOR strongly correlate with pCamKIIα-Thr286 levels in nEVs from HD, while this association is lost in DS individuals, suggesting that the aberrant activation of the Akt/mTOR axis may contribute to dysfunctional synaptic plasticity mechanisms in DS through CaMKIIα.

Conclusions

The alteration of the insulin signalling/mTOR pathways represents an early event in DS brain and likely contributes to the cerebral dysfunctions and intellectual disability observed in this unique population.

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