Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly population and has worldwide impact. The etiology of the disease is complex and results from the confluence of multiple mechanisms ultimately leading to neuronal loss and cognitive decline. Among risk factors, aging is the most relevant and accounts for several pathogenic events that contribute to disease-specific toxic mechanisms. Accumulating evidence linked the alterations of the mammalian target of rapamycin (mTOR), a serine/threonine protein kinase playing a key role in the regulation of protein synthesis and degradation, to age-dependent cognitive decline and pathogenesis of AD. To date, growing studies demonstrated that aberrant mTOR signaling in the brain affects several pathways involved in energy metabolism, cell growth, mitochondrial function and proteostasis. Recent advances associated alterations of the mTOR pathway with the increased oxidative stress. Disruption of all these events strongly contribute to age-related cognitive decline including AD. The current review discusses the main regulatory roles of mTOR signaling network in the brain, focusing on its role in autophagy, oxidative stress and energy metabolism. Collectively, experimental data suggest that targeting mTOR in the CNS can be a valuable strategy to prevent/slow the progression of AD.

mTOR in Alzheimer disease and its earlier stages: Links to oxidative damage in the progression of this dementing disorder / Perluigi, M.; Di Domenico, F.; Barone, E.; Butterfield, D. A.. - In: FREE RADICAL BIOLOGY & MEDICINE. - ISSN 0891-5849. - 169:(2021), pp. 382-396. [10.1016/j.freeradbiomed.2021.04.025]

mTOR in Alzheimer disease and its earlier stages: Links to oxidative damage in the progression of this dementing disorder

Perluigi M.;Di Domenico F.;Barone E.;
2021

Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly population and has worldwide impact. The etiology of the disease is complex and results from the confluence of multiple mechanisms ultimately leading to neuronal loss and cognitive decline. Among risk factors, aging is the most relevant and accounts for several pathogenic events that contribute to disease-specific toxic mechanisms. Accumulating evidence linked the alterations of the mammalian target of rapamycin (mTOR), a serine/threonine protein kinase playing a key role in the regulation of protein synthesis and degradation, to age-dependent cognitive decline and pathogenesis of AD. To date, growing studies demonstrated that aberrant mTOR signaling in the brain affects several pathways involved in energy metabolism, cell growth, mitochondrial function and proteostasis. Recent advances associated alterations of the mTOR pathway with the increased oxidative stress. Disruption of all these events strongly contribute to age-related cognitive decline including AD. The current review discusses the main regulatory roles of mTOR signaling network in the brain, focusing on its role in autophagy, oxidative stress and energy metabolism. Collectively, experimental data suggest that targeting mTOR in the CNS can be a valuable strategy to prevent/slow the progression of AD.
2021
Alzheimer's disease; mTOR; oxidative stress; protein aggregation; proteostasis; aged; autophagy; humans; signal transduction; TOR serine-threonine kinases; Alzheimer disease
01 Pubblicazione su rivista::01a Articolo in rivista
mTOR in Alzheimer disease and its earlier stages: Links to oxidative damage in the progression of this dementing disorder / Perluigi, M.; Di Domenico, F.; Barone, E.; Butterfield, D. A.. - In: FREE RADICAL BIOLOGY & MEDICINE. - ISSN 0891-5849. - 169:(2021), pp. 382-396. [10.1016/j.freeradbiomed.2021.04.025]
File allegati a questo prodotto
File Dimensione Formato  
Perluigi_mTOR in Alzheimer_2021.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 2.63 MB
Formato Adobe PDF
2.63 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1610951
Citazioni
  • ???jsp.display-item.citation.pmc??? 39
  • Scopus 71
  • ???jsp.display-item.citation.isi??? 68
social impact