Insulin activated Akt rescues Aβ oxidative stress-induced cell death by orchestrating molecular trafficking.

Valeria Vetri, Valeria Militello, Pasquale Picone, Rita Carrotta, Pier Luigi San Biagio, Daniela Giacomazza, Marta Di Carlo

Risultato della ricerca: Articlepeer review

50 Citazioni (Scopus)

Abstract

Increasing evidence indicates that Alzheimer's disease, one of the most diffused aging pathologies, and diabetes may be related. Here, we demonstrate that insulin signalling protects LAN5 cells by amyloid-β42 (Aβ)-induced toxicity. Aβ affects both activation of insulin receptors and the levels of phospho-Akt, a critical signalling molecule in this pathway. In contrast, oxidative stress induced by Aβ can be antagonized by active Akt that, in turn, inhibits Foxo3a, a pro-apoptotic transcription factor activated by reactive oxygen species generation. Insulin cascade protects against mitochondrial damage caused by Aβ treatment, restoring the mitochondrial membrane potential. Moreover, we show that the recovery of the organelle integrity recruits active Akt translocation to the mitochondrion. Here, it plays a role both by maintaining unimpaired the permeability transition pore through increase in HK-II levels and by blocking apoptosis through phosphorylation of Bad, coming from cytoplasm after Aβ stimulus. Together, these results indicate that the Akt survival signal antagonizes the Aβ cell death process by balancing the presence and modifications of common molecules in specific cellular environments.
Lingua originaleEnglish
pagine (da-a)832-843
Numero di pagine12
RivistaAging Cell
Volume10
Stato di pubblicazionePublished - 2011

All Science Journal Classification (ASJC) codes

  • Ageing
  • Cell Biology

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