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J Zhejiang Univ (Med Sci)  2020, Vol. 49 Issue (1): 100-106    DOI: 10.3785/j.issn.1008-9292.2020.02.10
    
Poly adenosine diphosphate-ribosylation and neurodegenerative diseases
WANG Yi(),LU Yunbi*()
Department of Pharmacology, College of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China
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Abstract  

The morbidity of neurodegenerative diseases are increased in recent years, however, the treatment is limited. Poly ADP-ribosylation (PARylation) is a post-translational modification of protein that catalyzed by poly(ADP-ribose) polymerase (PARP). Studies have shown that PARylation is involved in many neurodegenerative diseases such as stroke, Parkinson's diseases, Alzheimer's disease, amyotrophic lateral sclerosis and so on, by affecting intracellular translocation of protein molecules, protein aggregation, protein activity, and cell death. PARP inhibitors have showed neuroprotective efficacy for neurodegenerative diseases in pre-clinical studies and phase Ⅰ clinical trials. To find new PARP inhibitors with more specific effects and specific pharmacokinetic characteristics will be the new direction for the treatment of neurodegenerative diseases. This paper reviews the recent progress on PARylation in neurodegenerative diseases.



Key wordsPoly ADP ribosylation      Poly(ADP-ribose) polymerases      Neurodegeneration      Enzyme inhibitor/therapies      Review     
Received: 05 September 2019      Published: 08 June 2020
CLC:  R741  
Corresponding Authors: LU Yunbi     E-mail: 182486@zju.edu.cn;yunbi@zju.edu.cn
Cite this article:

WANG Yi,LU Yunbi. Poly adenosine diphosphate-ribosylation and neurodegenerative diseases. J Zhejiang Univ (Med Sci), 2020, 49(1): 100-106.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2020.02.10     OR     http://www.zjujournals.com/med/Y2020/V49/I1/100


多腺苷二磷酸核糖基化修饰与神经退行性变性疾病

神经退行性疾病的发病率越来越高,但其治疗手段有限。多腺苷二磷酸核糖基化修饰(PARylation)是由多腺苷二磷酸核糖聚合酶(PARP)催化的蛋白质翻译后修饰。PARylation通过影响蛋白质在细胞内的移位、聚集、蛋白质活性和细胞死亡,参与脑卒中、帕金森病、阿尔茨海默病、运动神经元病等神经退行性变性疾病的发生和发展。PARP抑制剂通过抑制蛋白PARylation,在药物临床前试验和临床试验Ⅰ期都展现了明显的神经保护作用。然而,寻找作用更特异的、符合神经退行性变性疾病治疗药动学特点的新型PARP抑制剂,将是抗神经退行性药物研发的新方向。本文就PARylation与神经退行性变性疾病的研究进展作一综述。


关键词: 多聚ADP-核糖化作用,  聚ADP核糖聚合酶类,  神经退行性疾病,  酶抑制剂/治疗,  综述 
Fig 1 The role of poly ADP-ribosylation (PARylation) in neurodegenerative diseases
[1]   BASELLO D A , SCOVASSI A I . Poly(ADP-ribosylation) and neurodegenerative disorders[J]. Mitochondrion, 2015, 24:56- 63
doi: 10.1016/j.mito.2015.07.005
[2]   WU Y , CHEN M , JIANG J . Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling[J]. Mitochondrion, 2019, 49:35- 45
doi: 10.1016/j.mito.2019.07.003
[3]   CHAMBON P , WEILL J D , MANDEL P . Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme[J]. Biochem Biophys Res Commun, 1963, 11:39- 43
doi: 10.1016/0006-291x(63)90024-x
[4]   COSI C , SUZUKI H , MILANI D et al. Poly(ADP-ribose) polymerase:early involvement in glutamate-induced neurotoxicity in cultured cerebellar granule cells[J]. J Neurosci Res, 1994, 39 (1): 38- 46
doi: 10.1002/jnr.490390106
[5]   ZHANG J , DAWSON V L , DAWSON T M et al. Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity[J]. Science, 1994, 263 (5147): 687- 689
doi: 10.1126/science.8080500
[6]   GERACE E , PELLEGRINI-GIAMPIETRO D E , MORONI F et al. Poly(ADP-ribose)polymerase 1(PARP-1) activation and Ca(2+) permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) channels in post-ischemic brain damage:New therapeutic opportunities?[J]. CNS Neurol Disord Drug Targets, 2015, 14 (5): 636- 646
doi: 10.2174/1871527314666150430162841
[7]   KHODYREVA S N, LAVRIK O I.[Poly(ADP-Ribose) polymerase 1 as a key regulator of DNA repair] [J]. Mol Biol (Mosk), 2016, 50(4): 655-673. DOI: 10.7868/S0026898416040030.
[8]   PIAO L , FUJIOKA K , NAKAKIDO M et al. Regulation of poly(ADP-Ribose) polymerase 1 functions by post-translational modifications[J]. Front Biosci (Landmark Ed), 2018, 23:13- 26
doi: 10.2741/4578
[9]   MCGURK L , RIFAI O M , BONINI N M . Poly(ADP-ribosylation) in age-related neurological disease[J]. Trends Genet, 2019, 35 (8): 601- 613
doi: 10.1016/j.tig.2019.05.004
[10]   GAGNé J P , ISABELLE M , LO K S et al. Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes[J]. Nucleic Acids Res, 2008, 36 (22): 6959- 6976
doi: 10.1093/nar/gkn771
[11]   ANDRABI S A , UMANAH G K , CHANG C et al. Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis[J]. Proc Natl Acad Sci U S A, 2014, 111 (28): 10209- 10214
doi: 10.1073/pnas.1405158111
[12]   GUO L , FARE C M , SHORTER J . Therapeutic dissolution of aberrant phases by nuclear-import receptors[J]. Trends Cell Biol, 2019, 29 (4): 308- 322
doi: 10.1016/j.tcb.2018.12.004
[13]   TAYLOR J P , BROWN R H JR , CLEVELAND D W . Decoding ALS:from genes to mechanism[J]. Nature, 2016, 539 (7628): 197- 206
doi: 10.1038/nature20413
[14]   HOBSON E V , MCDERMOTT C J . Supportive and symptomatic management of amyotrophic lateral sclerosis[J]. Nat Rev Neurol, 2016, 12 (9): 526- 538
doi: 10.1038/nrneurol.2016.111
[15]   LIU C , FANG Y . New insights of poly(ADP-ribosylation) in neurodegenerative diseases:A focus on protein phase separation and pathologic aggregation[J]. Biochem Pharmacol, 2019, 167:58- 63
doi: 10.1016/j.bcp.2019.04.028
[16]   KIM S H , ENGELHARDT J I , HENKEL J S et al. Widespread increased expression of the DNA repair enzyme PARP in brain in ALS[J]. Neurology, 2004, 62 (2): 319- 322
doi: 10.1212/01.wnl.0000103291.04985.dc
[17]   KIM S H , HENKEL J S , BEERS D R et al. PARP expression is increased in astrocytes but decreased in motor neurons in the spinal cord of sporadic ALS patients[J]. J Neuropathol Exp Neurol, 2003, 62 (1): 88- 103
doi: 10.1093/jnen/62.1.88
[18]   MCGURK L , MOJSILOVIC-PETROVIC J , VAN DEERLIN V M et al. Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis[J]. Acta Neuropathol Commun, 2018, 6 (1): 84
doi: 10.1186/s40478-018-0586-1
[19]   MCGURK L , GOMES E , GUO L et al. Poly(ADP-ribose) prevents pathological phase separation of TDP-43 by promoting liquid demixing and stress granule localization[J]. Mol Cell, 2018, 71 (5): 703- 717
doi: 10.1016/j.molcel.2018.07.002
[20]   DUAN Y , DU A , GU J et al. PARylation regulates stress granule dynamics, phase separation, and neurotoxicity of disease-related RNA-binding proteins[J]. Cell Res, 2019, 29 (3): 233- 247
doi: 10.1038/s41422-019-0141-z
[21]   SINGATULINA A S , HAMON L , SUKHANOVA M V et al. PARP-1 activation directs FUS to DNA damage sites to form parg-reversible compartments enriched in damaged DNA[J]. Cell Rep, 2019, 27 (6): 1809- 1821
doi: 10.1016/j.celrep.2019.04.031
[22]   OUTEIRO T F , GRAMMATOPOULOS T N , ALTMANN S et al. Pharmacological inhibition of PARP-1 reduces alpha-synuclein- and MPP+-induced cytotoxicity in Parkinson's disease in vitro models[J]. Biochem Biophys Res Commun, 2007, 357 (3): 596- 602
doi: 10.1016/j.bbrc.2007.03.163
[23]   MANDIR A S , PRZEDBORSKI S , JACKSON-LEWIS V et al. Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced parkinsonism[J]. Proc Natl Acad Sci U S A, 1999, 96 (10): 5774- 5779
doi: 10.1073/pnas.96.10.5774
[24]   WANG H , SHIMOJI M , YU S W et al. Apoptosis inducing factor and PARP-mediated injury in the MPTP mouse model of Parkinson's disease[J]. Ann N Y Acad Sci, 2003, 991:132- 139
doi: 10.1111/j.1749-6632.2003.tb07471.x
[25]   WU X L , WANG P , LIU Y H et al. Effects of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide on blood-brain barrier and dopaminergic neurons of rats with lipopolysaccharide-induced Parkinson's disease[J]. J Mol Neurosci, 2014, 53 (1): 1- 9
doi: 10.1007/s12031-013-0175-5
[26]   KAM T I , MAO X , PARK H et al. Poly(ADP-ribose) drives pathologic alpha-synuclein neurodegeneration in Parkinson's disease[J]. Science, 2018, 362 (6414): pii:eaat8407
doi: 10.1126/science.aat8407
[27]   SARAIVA L M, SEIXAS DA SILVA G S, GALINA A, et al. Amyloid-beta triggers the release of neuronal hexokinase 1 from mitochondria[J/OL]. PLoS One, 2010, 5: e15230. DOI: 10.1371/journal.pone.0015230.
[28]   CORONA J C , GIMENEZ-CASSINA A , LIM F et al. Hexokinase Ⅱ gene transfer protects against neurodegeneration in the rotenone and MPTP mouse models of Parkinson's disease[J]. J Neurosci Res, 2010, 88 (9): 1943- 1950
doi: 10.1002/jnr.22357
[29]   FATOKUN A A , DAWSON V L , DAWSON T M . Parthanatos:mitochondrial-linked mechanisms and therapeutic opportunities[J]. Br J Pharmacol, 2014, 171 (8): 2000- 2016
doi: 10.1111/bph.12416
[30]   YU Y M , KIM J B , LEE K W et al. Inhibition of the cerebral ischemic injury by ethyl pyruvate with a wide therapeutic window[J]. Stroke, 2005, 36 (10): 2238- 2243
doi: 10.1161/01.STR.0000181779.83472.35
[31]   YING W , CHEN Y , ALANO C C et al. Tricarboxylic acid cycle substrates prevent PARP-mediated death of neurons and astrocytes[J]. J Cereb Blood Flow Metab, 2002, 22 (7): 774- 779
doi: 10.1097/00004647-200207000-00002
[32]   GALLUZZI L , VITALE I , AARONSON S A et al. Molecular mechanisms of cell death:recommendations of the Nomenclature Committee on Cell Death 2018[J]. Cell Death Differ, 2018, 25 (3): 486- 541
doi: 10.1038/s41418-017-0012-4
[33]   LI X , KLAUS J A , ZHANG J et al. Contributions of poly(ADP-ribose) polymerase-1 and -2 to nuclear translocation of apoptosis-inducing factor and injury from focal cerebral ischemia[J]. J Neurochem, 2010, 113 (4): 1012- 1022
doi: 10.1111/j.1471-4159.2010.06667.x
[34]   BIANCHETTI E, MLADINIC M, NISTRI A. Mechanisms underlying cell death in ischemia-like damage to the rat spinal cord in vitro[J/OL]. Cell Death Dis, 2013, 4: e707. DOI: 10.1038/cddis.2013.237.
[35]   YANG X , CHENG J , GAO Y et al. Downregulation of Iduna is associated with AIF nuclear translocation in neonatal brain after hypoxia-ischemia[J]. Neuroscience, 2017, 346:74- 80
doi: 10.1016/j.neuroscience.2017.01.010
[36]   MARTIRE S , MOSCA L , D'ERME M . PARP-1 involvement in neurodegeneration:A focus on Alzheimer's and Parkinson's diseases[J]. Mech Ageing Dev, 2015, 146-148:53- 64
doi: 10.1016/j.mad.2015.04.001
[37]   LEE Y , KANG H C , LEE B D et al. Poly (ADP-ribose) in the pathogenesis of Parkinson's disease[J]. BMB Rep, 2014, 47 (8): 424- 432
doi: 10.5483/bmbrep.2014.47.8.119
[38]   ANGLADE P , VYAS S , JAVOY-AGID F et al. Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease[J]. Histol Histopathol, 1997, 12 (1): 25- 31
[39]   BOYCHUK T M , NIKA O M , TKACHUK S S . The ratio of p53-proapoptotic and bcl-2 antiapoptotic activity in the hippocampus of rats with brain ischemia-reperfusion and experimental diabetes[J]. Fiziol Zh, 2016, 62 (6): 25- 33
doi: 10.15407/fz62.06.025
[40]   WESIERSKA-GADEK J , SCHMID G . Poly(ADP-ribose) polymerase-1 regulates the stability of the wild-type p53 protein[J]. Cell Mol Biol Lett, 2001, 6 (2): 117- 140
doi: 10.1046/j.1462-5822.2001.00094.x
[41]   MARTIRE S, FUSO A, ROTILI D, et al. PARP-1 modulates amyloid beta peptide-induced neuronal damage[J/OL]. PLoS One, 2013, 8(9): e72169. DOI: 10.1371/journal.pone.0072169.
[42]   ZHOU J , JI M , YAO H et al. Discovery of quinazoline-2, 4(1H, 3H)-dione derivatives as novel PARP-1/2 inhibitors:design, synthesis and their antitumor activity[J]. Org Biomol Chem, 2018, 16 (17): 3189- 3202
doi: 10.1039/c8ob00286j
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