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PARIS farnesylation prevents neurodegeneration in models of Parkinson's disease

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

  2. Author Address

    Sungkyunkwan Univ, Samsung Biomed Res Inst, Dept Pharmacol, Sch Med, Suwon 16419, South Korea.Johns Hopkins Univ, Inst Cell Engn, Neuroregenerat & Stem Cell Programs, Sch Med, Baltimore, MD 21205 USA.Johns Hopkins Univ, Dept Physiol, Sch Med, Baltimore, MD 21205 USA.Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21205 USA.Adrienne Helis Malvin Med Res Fdn, New Orleans, LA 70130 USA.Diana Helis Henry Med Res Fdn, New Orleans, LA 70130 USA.Johns Hopkins Univ, Dept Pharmacol & Mol Sci, Sch Med, Baltimore, MD 21205 USA.NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21705 USA.Ajou Univ, Dept Physiol, Sch Med, Suwon 16499, South Korea.Kyung Hee Univ, Neurodegenerat Control Res Ctr, Dept Neurosci, Dept Physiol,Sch Med, Seoul 02447, South Korea.Sungkyunkwan Univ, Samsung Biomed Res Inst, Res Core Facil, Sch Med, Suwon 16419, South Korea.Sungkyunkwan Univ, Samsung Med Ctr, Dept Neurol, Sch Med, Seoul 06351, South Korea.Seoul Natl Univ, Dept Neurosurg, Coll Med, Seoul 03080, South Korea.Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21205 USA.Sungkyunkwan Univ, Samsung Med Ctr, Samsung Biomed Res Inst, Sch Med, Seoul 06351, South Korea.NINDS, Div Neurosci, NIH, Bethesda, MD 20892 USA.Daegu Geongbuk Inst Sci & Technol DGIST, Well Aging Res Ctr, Div Biotechnol, Daegu 42988, South Korea.Univ Alabama Birmingham, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA.YEPBio Co Ltd, Nat Bioact & Anticanc Res Inst, Anyang 14056, South Korea.
    1. Year: 2021
    2. Date: Jul 28
  2. Journal: Science translational medicine
  3. AMER ASSOC ADVANCEMENT SCIENCE,
    1. 13
    2. 604
  5. Type of Article: Article
  6. Article Number: eaax8891
  7. ISSN: 1946-6234
  1. Abstract:

    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-1 alpha (PGC-1 alpha; PPARGC1A) activity. Here, we identify farnesol as an inhibitor of PARIS. Farnesol promoted the farnesylation of PARIS, preventing its repression of PGC-1 alpha 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-1 alpha activity.

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External Sources

  1. View Full Text
  2. DOI: 10.1126/scitranslmed.aax8891
  3. PMID: 34321320
  4. View record in Web of Science®
  5. WOS: 000678685100002

Library Notes

  1. Fiscal Year: FY2020-2021
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