Poly (ADP-ribose) Interacts With Phosphorylated α-Synuclein in Post Mortem PD Samples
Laura N. Puentes,Zsofia Lengyel-Zhand,Ji Youn Lee,Chia-Ju Hsieh,Mark E. Schneider,Kimberly J. Edwards,Kelvin C. Luk,Virginia M.-Y. Lee,John Q. Trojanowski,Robert H. Mach +9 more
TLDR
In this article, the PAR-pαSyn interactions were investigated using immunofluorescence-based assays to explore if PAR-1 enzymatic product (PAR) promotes the aberrant cytoplasmic accumulation of pαSyn.Abstract:
Poly (ADP-ribose) (PAR) is a negatively charged polymer that is biosynthesized by Poly (ADP-ribose) Polymerase-1 (PARP-1) and regulates various cellular processes. Alpha-synuclein (αSyn) is an intrinsically disordered protein (IDP) that has been directly implicated with driving the onset and progression of Parkinson's disease (PD). The mechanisms by which α-synuclein (αSyn) elicits its neurotoxic effects remain unclear, though it is well established that the main components of Lewy bodies (LBs) and Lewy neurites (LNs) in PD patients are aggregated hyperphosphorylated (S129) forms of αSyn (pαSyn). In the present study, we used immunofluorescence-based assays to explore if PARP-1 enzymatic product (PAR) promotes the aberrant cytoplasmic accumulation of pαSyn. We also performed quantitative measurements using in situ proximity ligation assays (PLA) on a transgenic murine model of α-synucleinopathy (M83-SNCA∗A53T) and post mortem PD/PDD patient samples to characterize PAR-pαSyn interactions. Additionally, we used bioinformatic approaches and site-directed mutagenesis to identify PAR-binding regions on αSyn. In summary, our studies show that PAR-pαSyn interactions are predominantly observed in PD-relevant transgenic murine models of αSyn pathology and post mortem PD/PDD patient samples. Moreover, we confirm that the interactions between PAR and αSyn involve electrostatic forces between negatively charged PAR and lysine residues on the N-terminal region of αSyn.read more
Citations
More filters
Journal ArticleDOI
Interaction of Mitochondrial Calcium and ROS in Neurodegeneration
Artyom Y. Baev,Andrey Y. Vinokurov,Irina N. Novikova,Viktor Dremin,Elena Potapova,Andrey Y. Abramov +5 more
TL;DR: The latest literature on the crosstalk of reactive oxygen species and Ca2+ in brain mitochondria in physiology and beyond is reviewed, considering how changes in mitochondrial metabolism or redox signaling can convert this interaction into a pathological event.
Journal ArticleDOI
Dl-3-n-Butylphthalide Rescues Dopaminergic Neurons in Parkinson’s Disease Models by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment
Rongfang Que,Jialing Zheng,Zihan Chang,Wenjie Zhang,Hualing Li,Zhenchao Xie,Zifeng Huang,Hai-Tao Wang,Jiangping Xu,Dana Jin,Wanlin Yang,Eng-King Tan,Qing Wang +12 more
Journal ArticleDOI
Neurodegeneration and Neuroinflammation in Parkinson’s Disease: a Self-Sustained Loop
TL;DR: In this paper , an up-to-date summary of the main cellular alterations underlying neuroinflammation in Parkinson's disease, including those induced by environmental factors and those related to the genetic background of affected patients.
Journal ArticleDOI
Neuroprotective Effects of PARP Inhibitors in Drosophila Models of Alzheimer’s Disease
A. Della Maggiore,Assunta Maria Casale,Walter Toscanelli,Ugo Cappucci,Dante Rotili,Maddalena Grieco,Jean-Philippe Gagné,Guy G. Poirier,Maria D'Erme,Lucia Piacentini +9 more
TL;DR: It is found that both pharmacological inhibition and genetic inactivation of PARP-1 significantly extend lifespan and improve the climbing ability of transgenic AD flies and Interestingly, olaparib and MC2050 also suppress the AD-associated aberrant activation of transposable elements in neuronal tissues of AD flies.
Journal ArticleDOI
Revisiting the miR-200 Family: A Clan of Five Siblings with Essential Roles in Development and Disease
TL;DR: The indispensable role of the miR-200 family in governing the cellular functions associated with epithelial homeostasis, such as epithelial differentiation and neurogenesis is elaborated, and the application of these small biomolecules in aiding early cancer detection and intervention is elaborated.
References
More filters
Journal ArticleDOI
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
Garrett M. Morris,Ruth Huey,William Lindstrom,Michel F. Sanner,Richard K. Belew,David S. Goodsell,Arthur J. Olson +6 more
TL;DR: AutoDock4 incorporates limited flexibility in the receptor and its utility in analysis of covalently bound ligands is reported, using both a grid‐based docking method and a modification of the flexible sidechain technique.
Journal ArticleDOI
Alpha-synuclein in Lewy bodies.
Maria Grazia Spillantini,Marie L. Schmidt,Virginia M.-Y. Lee,John Q. Trojanowski,Ross Jakes,Michel Goedert +5 more
TL;DR: Strong staining of Lewy bodies from idiopathic Parkinson's disease with antibodies for α-synuclein, a presynaptic protein of unknown function which is mutated in some familial cases of the disease, indicates that the LewY bodies from these two diseases may have identical compositions.
Journal ArticleDOI
Diagnosis and management of dementia with Lewy bodies Fourth consensus report of the DLB Consortium
Ian G. McKeith,Bradley F. Boeve,Dennis W. Dickson,Glenda M. Halliday,John-Paul Taylor,Daniel Weintraub,Dag Aarsland,Dag Aarsland,James E. Galvin,Johannes Attems,Johannes Attems,Clive Ballard,Clive Ballard,Ashley Bayston,Ashley Bayston,Thomas G. Beach,Thomas G. Beach,Frédéric Blanc,Nicolaas Bohnen,Nicolaas Bohnen,Nicolaas Bohnen,Laura Bonanni,Laura Bonanni,Jose Bras,Jose Bras,Patrik Brundin,Patrik Brundin,David J. Burn,David J. Burn,Alice Chen-Plotkin,John E. Duda,Omar M. A. El-Agnaf,Howard Feldman,Tanis J. Ferman,Dominic Ffytche,Hiroshige Fujishiro,Douglas Galasko,Jennifer G. Goldman,Stephen N. Gomperts,Neill R. Graff-Radford,Lawrence S. Honig,Lawrence S. Honig,Alex Iranzo,Alex Iranzo,Alex Iranzo,Kejal Kantarci,Daniel I. Kaufer,Walter Kukull,Virginia M.Y. Lee,James B. Leverenz,James B. Leverenz,Simon J.G. Lewis,Carol F. Lippa,Carol F. Lippa,Angela Lunde,M Masellis,M Masellis,M Masellis,Eliezer Masliah,Pamela J. McLean,Brit Mollenhauer,Brit Mollenhauer,Thomas J. Montine,Thomas J. Montine,Emilio Moreno,Emilio Moreno,Emilio Moreno,Etsuro Mori,Etsuro Mori,Etsuro Mori,Melissa E. Murray,John T. O'Brien,John T. O'Brien,Sotoshi Orimo,Sotoshi Orimo,Ronald B. Postuma,Ronald B. Postuma,Shankar Ramaswamy,Shankar Ramaswamy,Owen A. Ross,David P. Salmon,David P. Salmon,Andrew B. Singleton,Andrew B. Singleton,Angela Taylor,Angela Taylor,Alan Thomas,Pietro Tiraboschi,Jon B. Toledo,John Q. Trojanowski,Debby W. Tsuang,Zuzana Walker,Zuzana Walker,Masahito Yamada,Masahito Yamada,Kenji Kosaka +95 more
TL;DR: The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade.
Journal ArticleDOI
CellProfiler 3.0: Next-generation image processing for biology.
Claire McQuin,Allen Goodman,Vasiliy S. Chernyshev,Vasiliy S. Chernyshev,Lee Kamentsky,Beth A. Cimini,Kyle W. Karhohs,Minh Doan,Liya Ding,Susanne M. Rafelski,Derek Thirstrup,Winfried Wiegraebe,Shantanu Singh,Tim Becker,Juan C. Caicedo,Anne E. Carpenter +15 more
TL;DR: CellProfiler 3.0 is described, a new version of the software supporting both whole-volume and plane-wise analysis of three-dimensional image stacks, increasingly common in biomedical research.
Journal ArticleDOI
The many faces of α-synuclein: from structure and toxicity to therapeutic target
TL;DR: An overview of current knowledge and prevailing hypotheses regarding the conformational, oligomerization and aggregation states of α-syn and their role in regulating α- synuclein function in health and disease is provided.
Related Papers (5)
Multiple system atrophy-associated oligodendroglial protein p25α stimulates formation of novel α-synuclein strain with enhanced neurodegenerative potential
Nelson Ferreira,Hjalte Gram,Zachary A. Sorrentino,Emil Gregersen,Sissel Ida Schmidt,Lasse Reimer,Cristine Betzer,Clara Perez-Gozalbo,Marjo Beltoja,Madhu Nagaraj,Jie Wang,Jie Wang,Jan Stanislaw Nowak,Mingdong Dong,Katarina Willén,Ersoy Cholak,Kaare Bjerregaard-Andersen,Nicolas Mendez,Prakruti Rabadia,Mohammad Shahnawaz,Claudio Soto,Daniel E. Otzen,Ümit Akbey,Morten Meyer,Benoit I. Giasson,Marina Romero-Ramos,Poul Henning Jensen +26 more
The neurotoxin, MPP+, induces hyperphosphorylation of Tau, in the presence of alpha-Synuclein, in SH-SY5Y neuroblastoma cells.
Tetyana Duka,Anita Sidhu +1 more