Abstract:
:Numerous studies have reported that inhibition of MTOR (mechanistic target of rapamycin kinase) clearly reduces Alzheimer disease neuropathological hallmarks in mouse models. This has resulted in calls for the use of the MTOR inhibitor rapamycin for the treatment of dementia in humans. Unfortunately, intervention with rapamycin in these mouse studies commenced before or early in the appearance of these pathological hallmarks. Later in Alzheimer disease, when dementia actually manifests, the brain's lysosomal system is severely damaged and treatment with rapamycin is likely to exacerbate this damage. We reassess literature described by a recent perspective article calling for the use of MTOR inhibition in dementia and conclude that rapamycin could be useful, but only in people who are in the earliest stages of Alzheimer disease. We contend that our interpretation of preclinical data concerning use of rapamycin in Alzheimer disease models is necessary if we are to avoid another failed Alzheimer disease drug trial. Abbreviations: AD: Alzheimer disease; APP: amyloid beta precursor protein; MAPT: microtubule associated protein tau; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1.
journal_name
Autophagyjournal_title
Autophagyauthors
Carosi JM,Sargeant TJdoi
10.1080/15548627.2019.1615823subject
Has Abstractpub_date
2019-08-01 00:00:00pages
1460-1462issue
8eissn
1554-8627issn
1554-8635journal_volume
15pub_type
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