Fibrates inhibit the apoptosis of Batten disease lymphoblast cells via autophagy recovery and regulation of mitochondrial membrane potential

  • Minho Hong
  • Ki Duk Song
  • Hak-Kyo Lee
  • SunShin Yi
  • Yong Seok Lee
  • Tae-Hwe Heo
  • Hyun Sik Jun
  • Sung-Jo Kim


Batten disease (BD; also known as juvenile neuronal ceroid lipofuscinosis) is a genetic disorder inherited as an autosomal recessive trait and is characterized by blindness, seizures, cognitive decline, and early death resulting from the inherited mutation of the CLN3 gene. Mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, disrupted autophagy, and enhanced apoptosis have been suggested to play a role in BD pathogenesis. Fibrates, a class of lipid-lowering drugs that induce peroxisome proliferator-activated receptor-α (PPAR-α) activation, are the most commonly used PPAR agonists. Assuming that fibrates have a neuroprotective effect, we studied the effects of fibrates, fenofibrate, bezafibrate, and gemfibrozil on apoptosis, depolarization of mitochondrial membrane, and defective autophagy in BD lymphoblast cells. The viability of fibrate-treated BD lymphoblast cells increased to levels of normal lymphoblast cells. In addition, treatment with fibrates inhibited depolarization of mitochondrial membrane potential in BD lymphoblast cells. Defective autophagy in BD lymphoblast cells was normalized when treated with fibrates as indicated by increased acridine orange staining. The recovery of autophagy in BD lymphoblast cells is most likely attributed to the upregulation of autophagy proteins, lysosomal-associated membrane protein 1 (LAMP1), and LC3 I/II, after treatment with fibrates. This study therefore suggests that fibrates may have a therapeutic potential against BD.


Autophagy Mitochondria PPAR-α Lymphoblast Batten disease 



This research was supported by the Academic Research fund of Hoseo University in 2012 (2012-0256)


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Copyright information

© The Society for In Vitro Biology 2015

Authors and Affiliations

  • Minho Hong
    • 1
  • Ki Duk Song
    • 2
  • Hak-Kyo Lee
    • 2
  • SunShin Yi
    • 3
  • Yong Seok Lee
    • 4
  • Tae-Hwe Heo
    • 5
  • Hyun Sik Jun
    • 6
  • Sung-Jo Kim
    • 1
  1. 1.Department of BiotechnologyHoseo UniversityAsanRepublic of Korea
  2. 2.Department of Animal BiotechnologyChonbuk National UniversityJeonjuRepublic of Korea
  3. 3.Department of Biomedical Laboratory Science, College of Biomedical SciencesSoonchunhyang UniversityAsanRepublic of Korea
  4. 4.Department of Life Science and BiotechnologySoonchunhyang UniversityAsanRepublic of Korea
  5. 5.Lab of Immunology, Integrated Research Institute of Pharmaceutical Sciences, College of PharmacyThe Catholic University of KoreaBucheonRepublic of Korea
  6. 6.Department of Biotechnology and Bioinformatics, College of Science and TechnologyKorea UniversitySejongRepublic of Korea

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