Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease

• DOI: 10.1126/science.aat8407
• Publication Date: 2018-11-01T18:04:41Z
• Authors: Tae-In Kam; Xiaobo Mao; Hyejin Park; Shih-Ching Chou; Senthilkumar S. K...; George Essien Umanah; Seung Pil Yun; Saurav Brahmachari; Nikhil Panicker; Rong Chen; Shaida A. Andrabi; Chen Qi; Guy G. Poirier; Olga Pletnikova; Juan C. Troncoso; Lynn M. Bekris; James B. Leverenz; Alexander Pantelyat; Han Seok Ko; Liana S. Rosenthal; Ted M. Dawson; Valina L. Dawson
• Keywords: Pathogenesis

PAR promotes α-synuclein toxicity How pathologic (α-syn) leads to neurodegeneration in Parkinson's disease (PD) remains poorly understood. Kam et al. studied the α-syn preformed fibril (α-syn PFF) model of sporadic PD (see Perspective by Brundin and Wyse). They found that α-syn–activated poly(adenosine 5′-diphosphate–ribose) (PAR) polymerase–1 (PARP-1) inhibition PARP or knockout PARP-1 protected mice from pathology. The generation PFF–induced activation converted PFF a strain was 25-fold more toxic, termed PAR–α-syn PFF. An increase cerebrospinal fluid evidence substantia nigra patients indicates contributes pathogenesis through parthanatos conversion toxic strain. Science , this issue p. eaat8407 ; see also 521