Should evidence of an autolysosomal de-acidification defect in Alzheimer and Parkinson diseases call for caution in prescribing chronic PPI and DMARD?

ABSTRACT: Nearly fifty million older people suffer from neurodegenerative diseases, including Alzheimer (AD) and Parkinson (PD) disease, a global burden expected to triple by 2050. Such an imminent "neurological pandemic" urges the identification of environmental risk factors that are hopefully avoided to fight the disease. In 2022, strong evidence in mouse models incriminated defective lysosomal acidification and impairment of the autophagy pathway as modifiable risk factors for dementia. To date, the most prescribed lysosomotropic drugs are proton pump inhibitors (PPIs), chloroquine (CQ), and the related hydroxychloroquine (HCQ), which belong to the group of disease-modifying antirheumatic drugs (DMARDs). This commentary aims to open the discussion on the possible mechanisms connecting the long-te

SUBMITTER: Giuliano S 

PROVIDER: S-EPMC10472882 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature