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

Area of Science:

• Neuroscience
• Cellular Biology
• Pharmacology

Background:

• The mechanistic target of rapamycin (mTOR) pathway regulates critical cellular functions in the brain.
• Dysregulation of the mTOR pathway is implicated in numerous neurological disorders, including Alzheimer's disease (AD).
• In AD, aberrant mTOR signaling impairs autophagy, leading to the accumulation of amyloid-beta (Aβ) and tau aggregates, and disrupts neuronal metabolism.

Purpose of the Study:

• To review current findings on the therapeutic application of mTOR inhibitors in Alzheimer's disease treatment.
• To evaluate the potential of mTOR inhibitors in mitigating AD pathology and restoring cognitive deficits.

Main Methods:

• Comprehensive literature review of studies investigating mTOR inhibitors (rapamycin and rapalogs) in the context of AD.
• Analysis of preclinical and clinical data on the efficacy of mTOR inhibitors in reducing AD hallmarks and improving cognitive performance.

Main Results:

• Current evidence suggests that mTOR inhibitors can effectively reduce AD hallmarks, such as Aβ and tau pathology.
• These inhibitors have demonstrated the potential to recover cognitive performances in AD models.
• Rapamycin and its analogs show promise as therapeutic agents for AD.

Conclusions:

• mTOR inhibitors represent a potential therapeutic strategy for counteracting Alzheimer's disease.
• Further investigation is required to fully elucidate the role of aberrant mTOR signaling in AD.
• Standardization of therapeutic approaches involving mTOR inhibitors is necessary for successful translation to human clinical practice.