Abstract：
:Neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Huntington's disease manifest with the neuronal accumulation of toxic proteins. Since autophagy upregulation enhances the clearance of such proteins and ameliorates their toxicities in animal models, we and others have sought to re-position/re-profile existing compounds used in humans to identify those that may induce autophagy in the brain. A key challenge with this approach is to assess if any hits identified can induce neuronal autophagy at concentrations that would be seen in humans taking the drug for its conventional indication. Here we report that felodipine, an L-type calcium channel blocker and anti-hypertensive drug, induces autophagy and clears diverse aggregate-prone, neurodegenerative disease-associated proteins. Felodipine can clear mutant α-synuclein in mouse brains at plasma concentrations similar to those that would be seen in humans taking the drug. This is associated with neuroprotection in mice, suggesting the promise of this compound for use in neurodegeneration.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Siddiqi FH,Menzies FM,Lopez A,Stamatakou E,Karabiyik C,Ureshino R,Ricketts T,Jimenez-Sanchez M,Esteban MA,Lai L,Tortorella MD,Luo Z,Liu H,Metzakopian E,Fernandes HJR,Bassett A,Karran E,Miller BL,Fleming A,Rubinszteidoi
10.1038/s41467-019-09494-2subject
Has Abstractpub_date
2019-04-18 00:00:00pages
1817issue
1issn
2041-1723pii
10.1038/s41467-019-09494-2journal_volume
10pub_type
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