Targeting mTOR to reduce Alzheimer-related cognitive decline: from current hits to future therapies

ABSTRACT

Introduction: 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.

KEYWORDS:

• mTOR
• Alzheimer disease
• rapamycin
• rapalogues
• autophagy

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by Fondi di Ateneo 2015 from Sapienza Università di Roma and SIR2014 (RBSI144MTL) from Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR) to F. Di Domenico. Authors state no conflict of interests.