| First Author | Jo A | Year | 2021 |
| Journal | Sci Transl Med | Volume | 13 |
| Issue | 604 | PubMed ID | 34321320 |
| Mgi Jnum | J:322197 | Mgi Id | MGI:6752491 |
| Doi | 10.1126/scitranslmed.aax8891 | Citation | Jo A, et al. (2021) PARIS farnesylation prevents neurodegeneration in models of Parkinson's disease. Sci Transl Med 13(604) |
| abstractText | Accumulation of the parkin-interacting substrate (PARIS; ZNF746), due to inactivation of parkin, contributes to Parkinson's disease (PD) through repression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha; PPARGC1A) activity. Here, we identify farnesol as an inhibitor of PARIS. Farnesol promoted the farnesylation of PARIS, preventing its repression of PGC-1alpha via decreasing PARIS occupancy on the PPARGC1A promoter. Farnesol prevented dopaminergic neuronal loss and behavioral deficits via farnesylation of PARIS in PARIS transgenic mice, ventral midbrain transduction of AAV-PARIS, adult conditional parkin KO mice, and the alpha-synuclein preformed fibril model of sporadic PD. PARIS farnesylation is decreased in the substantia nigra of patients with PD, suggesting that reduced farnesylation of PARIS may play a role in PD. Thus, farnesol may be beneficial in the treatment of PD by enhancing the farnesylation of PARIS and restoring PGC-1alpha activity. |
