PARIS farnesylation prevents neurodegeneration in models of Parkinson’s disease
Areum Jo, Yunjong Lee, Yunjong Lee, Tae‐In Kam, Sung-Ung Kang, Stewart Neifert, Senthilkumar S. Karuppagounder, Rin Khang, Hojin Kang, Hyejin Park, Shih-Ching Chou, Sungtaek Oh, Haisong Jiang, Deborah A. Swing, Sangwoo Ham, Sheila K. Pirooznia, George K. E. Umanah, Xiaobo Mao, Manoj Kumar, Han Seok Ko, Ho Chul Kang, Byoung Dae Lee, Yun-Il Lee, Yun-Il Lee, Shaida A. Andrabi, Chi‐Hu Park, Ji-Yeong Lee, Hanna Kim, Hye-In Kim, Hyojung Kim, Jin Whan Cho, Sun Ha Paek, Chan Hyun Na, Lino Tessarollo, Valina L. Dawson, Ted M. Dawson, Joo‐Ho Shin
Abstract
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 α-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-1α activity.