Targeting mTOR to reduce Alzheimer-related cognitive decline: from current hits to future therapies.
The mTOR pathway is involved in the regulation of a wide repertoire of cellular functions in the brain and its dysregulation is emerging as a leitmotif in a large number of neurological disorders. In AD, altered mTOR signaling contributes to the inhibition of autophagy deposition of Aβ and tau aggregates and to the alteration of several neuronal metabolic pathways. Areas covered: In this review, we report all the current findings on the use of mTOR inhibitors (rapamycin, rapalogues) in the treatment of AD. These results support the role of mTOR inhibitors as potential therapeutic agents able to reduce AD hallmarks and recover cognitive performances. Expert commentary: Despite mTOR inhibitors appearing to be ideal compounds to counteract AD, further studies are needed in order to gain knowledge on the involvement of aberrant mTOR in AD, and to standardize a valuable therapeutic approach that can be translated to humans.
a Department of Biochemical Sciences , Sapienza University of Rome , Rome , Italy.
Antonella
A
Tramutola
a Department of Biochemical Sciences , Sapienza University of Rome , Rome , Italy.
Chiara
C
Lanzillotta
a Department of Biochemical Sciences , Sapienza University of Rome , Rome , Italy.
Fabio
F
Di Domenico
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D060825:Cognitive Dysfunction; D006801:Humans; D058990:Molecular Targeted Therapy; D058570:TOR Serine-Threonine Kinases
C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
Alzheimer disease; autophagy; mTOR; rapalogues; rapamycin