title: Poly (ADP-ribose) in the pathogenesis of Parkinson's disease.
abstract: The defining feature of Parkinson's disease is a progressive and selective demise of dopaminergic neurons. A recent report on Parkinson's disease animal model demonstrates that poly (ADP-ribose) (PAR) dependent cell death, also named parthanatos, is accountable for selective dopaminergic neuronal loss. Parthanatos is a programmed necrotic cell death, characterized by PARP1 activation, apoptosis inducing factor (AIF) nuclear translocation, and large scale DNA fragmentation. Besides cell death regulation via interaction with AIF, PAR molecule mediates diverse cellular processes including genomic stability, cell division, transcription, epigenetic regulation, and stress granule formation. In this review, we will discuss the roles of PARP1 activation and PAR molecules in the pathological processes of Parkinson's disease. Potential interaction between PAR molecule and Parkinson's disease protein interactome are briefly introduced. Finally, we suggest promising points of therapeutic intervention in the pathological PAR signaling cascade to halt progression in Parkinson's disease.
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering; Departments of Physiology, and Neurology, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yunjong
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering; Departments of Neurology, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Ajou University School of Medicine, Suwon 443-721, Korea.
authors.forename: Ho Chul
authors.initials: HC
authors.lastname: Kang
authors.affiliation: Neurodegeneration Control Research Center, Department of Neuroscience, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Byoung Dae
authors.initials: BD
authors.lastname: Lee
authors.affiliation: Well Aging Research Center, Samsung Advanced Institute of Technology (SAIT), Suwon 443-803, Korea.
authors.forename: Yun-Il
authors.initials: YI
authors.lastname: Lee
authors.affiliation: Department of Bio-Engineering, Life Science RD Center, Sinil Pharmaceutical Co., Seoul 462-807, Korea.
authors.forename: Young Pil
authors.initials: YP
authors.lastname: Kim
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering; Departments of Neurology, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, Korea.
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Shin
mesh_terms: D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053938:DNA Fragmentation; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases