What is it about?
Intellectual disability, accelerated aging, and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). Although 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.
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Why is it important?
HIGHLIGHTS ∙ Brain insulin resistance develops early in Down syndrome (DS) independent of peripheral alterations. ∙ Brain insulin resistance is associated with mTOR hyperactivation in DS. ∙ Neuronal-derived extracellular vesicles (nEVs) allow detection of alterations of the insulin/mTOR pathway in DS brain. ∙ PTEN inhibition drives insulin/mTOR alterations in DS brain. ∙ Alterations of the insulin/mTOR pathway allow discrimination of DS versus healthy individuals. Clarification: - The mammalian target of rapamycin (mTOR) is a “master switch” between anabolic and catabolic cellular processes through regulating glucose metabolism, bioenergetics, mitochondrial function, and autophagy, also in response to insulin. - PTEN is a widely known negative regulator of insulin/PI3K signaling. - Crosstalk between insulin signaling and mTOR pathway has been indicated to play a key role in the maintenance of mindspan.
Perspectives
The alteration of the insulin-signaling/mTOR pathways represents an early event in DS brain and likely contributes to the cerebral dysfunction and intellectual disability observed in this unique population. The evaluation of nEVs content may be useful to identify novel targets for therapeutic interventions in DS. This aspect will be strengthened by performing additional studies to explore whether alterations identified through the analysis of nEVs associate with worse cognitive outcomes in DS. Roberto Matassa contributions was in providing electron microscopy imaging and the corresponding analysis.
Dr Roberto Matassa
Sapienza University of Rome
Read the Original
This page is a summary of: Aberrant crosstalk between insulin signaling and mTOR in young Down syndrome individuals revealed by neuronal‐derived extracellular vesicles, Alzheimer s & Dementia, November 2021, Wiley,
DOI: 10.1002/alz.12499.
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