Drug Res (Stuttg) 2023; 73(09): 491-505
DOI: 10.1055/a-2181-0813

A Review of PARP-1 Inhibitors: Assessing Emerging Prospects and Tailoring Therapeutic Strategies

Soundarya Ramesh
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, India
Shannon D Almeida
2   Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, India
Sameerana Hammigi
2   Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, India
Govardan Katta Radhakrishna
2   Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, India
Golla Sireesha
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, India
Theivendren Panneerselvam
3   Department of Pharmaceutical Chemistry, Swamy Vivekanandha College of Pharmacy, Elayampalayam, Tamil Nadu, India
Shangavi Vellingiri
4   Department of Pharmacy Practice, Swamy Vivekananda College of Pharmacy, Elayampalayam, Tamil Nadu, India
Selvaraj Kunjiappan
5   Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, Tamil Nadu, India
Damodar Nayak Ammunje
2   Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, India
Parasuraman Pavadai
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, India
› Author Affiliations


Eukaryotic organisms contain an enzyme family called poly (ADP-ribose) polymerases (PARPs), which is responsible for the poly (ADP-ribosylation) of DNA-binding proteins. PARPs are members of the cell signaling enzyme class. PARP-1, the most common isoform of the PARP family, is responsible for more than 90% of the tasks carried out by the PARP family as a whole. A superfamily consisting of 18 PARPs has been found. In order to synthesize polymers of ADP-ribose (PAR) and nicotinamide, the DNA damage nick monitor PARP-1 requires NAD+ as a substrate. The capability of PARP-1 activation to boost the transcription of proinflammatory genes, its ability to deplete cellular energy pools, which leads to cell malfunction and necrosis, and its involvement as a component in the process of DNA repair are the three consequences of PARP-1 activation that are of particular significance in the process of developing new drugs. As a result, the pharmacological reduction of PARP-1 may result in an increase in the cytotoxicity toward cancer cells.

Publication History

Received: 13 August 2023

Accepted: 18 September 2023

Article published online:
27 October 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Chandraprasad MS, Dey A, Swamy MK. Introduction to cancer and treatment approaches. In. Paclitaxel: Academic Press, Elsevier; 2022: 1-27
  • 2 Visone R, Croce CM. MiRNAs and cancer. Am J Pathol 2009; 174: 1131-1138
  • 3 Kocarnik JM, Compton K, Dean FE. et al. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: a systematic analysis for the global burden of disease study 2019. JAMA Oncol 2022; 8: 420-444
  • 4 Sathishkumar K, Chaturvedi M, Das P. et al. Cancer incidence estimates for 2022 & projection for 2025: Result from national cancer Registry Programme, India. Indian J Med Res 2022; 156: 598-607
  • 5 Hausman DM. What is cancer?. Perspect Biol Med 2019; 62: 778-784
  • 6 Sun YS, Zhao Z, Yang ZN. et al. Risk factors and preventions of breast cancer. Int J Biol Sci 2017; 13: 1387-1397
  • 7 Gangloff AR, Brown J, De Jong R. et al. Discovery of novel benzo [b][1, 4] oxazin-3 (4H)-ones as poly (ADP-ribose) polymerase inhibitors. Bioorganic Med Chem Lett 2013; 23: 4501-4505
  • 8 Costantino G, Pellicciari R. PARP Inhibitors As Anticancer Agents. Burger's Med Chem Drug Discov 2003; 151-174
  • 9 Chen W, Guo N, Qi M. et al. Discovery, mechanism and metabolism studies of 2, 3-difluorophenyl-linker-containing PARP1 inhibitors with enhanced in vivo efficacy for cancer therapy. Eur J Med Chem 2017; 138: 514-531
  • 10 Long H, Hu X, Wang B. et al. Discovery of Novel Apigenin–Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer. J Med Chem 2021; 64: 12089-12108
  • 11 Pescatore G, Branca D, Fiore F. et al. Identification and SAR of novel pyrrolo [1, 2-a] pyrazin-1 (2H)-one derivatives as inhibitors of poly (ADP-ribose) polymerase-1 (PARP-1). Bioorganic Med Chem Lett 2010; 20: 1094-1099
  • 12 Zhao H, Ji M, Cui G. et al. Discovery of novel quinazoline-2, 4 (1H, 3H)-dione derivatives as potent PARP-2 selective inhibitors. Bioorganic. Med Chem 2017; 25: 4045-4054
  • 13 Zmuda F, Malviya G, Blair A. et al. Synthesis and evaluation of a radioiodinated tracer with specificity for poly (ADP-ribose) polymerase-1 (PARP-1) in vivo. J Med Chem 2015; 58: 8683-8693
  • 14 Ye N, Chen CH, Chen T. et al. Design, synthesis, and biological evaluation of a series of benzo [de][1, 7] naphthyridin-7 (8 H)-ones bearing a functionalized longer chain appendage as novel PARP1 inhibitors. J Med Chem 2013; 56: 2885-2903
  • 15 Jones P, Altamura S, Boueres J. et al. Discovery of 2-{4-[(3 S)-piperidin-3-yl] phenyl}-2 H-indazole-7-carboxamide (MK-4827): a novel oral poly (ADP-ribose) polymerase (PARP) inhibitor efficacious in BRCA-1 and-2 mutant tumors. J Med Chem 2009; 52: 7170-7185
  • 16 Wang J, Li H, He G. et al. Discovery of novel dual poly (ADP-ribose) polymerase and phosphoinositide 3-kinase inhibitors as a promising strategy for cancer therapy. J Med Chem 2019; 63: 122-139
  • 17 Wang B, Chu D, Feng Y. et al. Discovery and Characterization of (8 S, 9 R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1 H-1, 2, 4-triazol-5-yl)-2, 7, 8, 9-tetrahydro-3 H-pyrido [4, 3, 2-de] phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly (ADP-ribose) Polymerase-1/2 Inhibitor, as an Anticancer Agent. J Med Chem 2016; 59: 335-357
  • 18 Jones P, Wilcoxen K, Rowley M. et al. Niraparib: a poly (ADP-ribose) polymerase (PARP) inhibitor for the treatment of tumors with defective homologous recombination. J Med Chem 2015; 58: 3302-3314
  • 19 Velagapudi UK, Langelier MF, Delgado-Martin C. et al. Design and synthesis of poly (ADP-ribose) polymerase inhibitors: impact of adenosine pocket-binding motif appendage to the 3-oxo-2, 3-dihydrobenzofuran-7-carboxamide on potency and selectivity. J Med Chem 2019; 62: 5330-5357
  • 20 Menear KA, Adcock C, Boulter R. et al. 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2 H-phthalazin-1-one: a novel bioavailable inhibitor of poly (ADP-ribose) polymerase-1. J Med Chem 2008; 51: 6581-6591
  • 21 Cockcroft XL, Dillon KJ, Dixon L. et al. Phthalazinones 2: Optimisation and synthesis of novel potent inhibitors of poly (ADP-ribose) polymerase. Bioorganic Med Chem Lett 2006; 16: 1040-1044
  • 22 Xie Z, Zhou Y, Zhao W. et al. Identification of novel PARP-1 inhibitors: Drug design, synthesis and biological evaluation. Bioorganic Med Chem Lett 2015; 25: 4557-4561
  • 23 Ferrigno F, Branca D, Kinzel O. et al. Development of substituted 6-[4-fluoro-3-(piperazin-1-ylcarbonyl) benzyl]-4, 5-dimethylpyridazin-3 (2H)-ones as potent poly (ADP–ribose) polymerase-1 (PARP-1) inhibitors active in BRCA deficient cells. Bioorganic Med Chem Lett 2010; 20: 1100-1105
  • 24 Leung M, Rosen D, Fields S. et al. Poly (ADP-ribose) polymerase-1 inhibition: preclinical and clinical development of synthetic lethality. Mol Med 2011; 17: 854-862
  • 25 Wang YQ, Wang PY, Wang YT. et al. An update on poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors: opportunities and challenges in cancer therapy. J Med Chem 2016; 59: 9575-9598
  • 26 v von Kobbe C, Harrigan JA, May A. et al. Central role for the Werner syndrome protein/poly (ADP-ribose) polymerase 1 complex in the poly (ADP-ribosyl) ation pathway after DNA damage. Mol Cell Biol 2003; 23: 8601-8613
  • 27 Wang Z, Wang F, Tang T. et al. The role of PARP1 in the DNA damage response and its application in tumor therapy. Front Med 2012; 6: 156-164
  • 28 Tirkkonen M, Johannsson O, Agnarsson BA. et al. Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations. Cancer Res 1997; 57: 1222-1227
  • 29 Mateo J, Lord CJ, Serra V. et al. A decade of clinical development of PARP inhibitors in perspective. Ann Oncol 2019; 30: 1437-1447
  • 30 Livraghi L, Garber JE. PARP inhibitors in the management of breast cancer: current data and future prospects. BMC Med 2015; 13: 1-16
  • 31 Matulonis UA, Oza AM, Ho TW. et al. Intermediate clinical endpoints: A bridge between progression-free survival and overall survival in ovarian cancer trials. Cancer 2015; 121: 1737-1746
  • 32 Gunderson CC, Moore KN. Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Future Oncol 2015; 11: 747-757
  • 33 Weaver AN, Yang ES. Beyond DNA repair: additional functions of PARP-1 in cancer. Front Oncol 2013; 3: 290
  • 34 McCabe N, Turner NC, Lord CJ. et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly (ADP-ribose) polymerase inhibition. Cancer Res 2006; 66: 8109-8115
  • 35 Garzon-Hernandez C, Ramirez-Merino N, Soberon MCM. Molecular Targeted Therapy in Oncology Focusing on DNA Repair Mechanisms. Arch Med Res 2022; 53: 807-817
  • 36 Friedlander M, Banerjee S, Mileshkin L. et al. Practical guidance on the use of olaparib capsules as maintenance therapy for women with BRCA mutations and platinum-sensitive recurrent ovarian cancer. Asia Pac J Clin Oncol 2016; 12: 323-331
  • 37 Scott LJ. Niraparib: first global approval. Drugs 2017; 77: 1029-1034
  • 38 Aghajanian C, Blank SV, Goff BA. et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 2012; 30: 2039-2045
  • 39 Pazzaglia S, Pioli C. Multifaceted role of PARP-1 in DNA repair and inflammation: pathological and therapeutic implications in cancer and non-cancer diseases. Cells 2019; 9: 41
  • 40 Karanika S, Karantanos T, Li L. et al. DNA damage response and prostate cancer: defects, regulation and therapeutic implications. Oncogene 2015; 34: 2815-2822
  • 41 Lheureux S, Braunstein M, Oza AM. Epithelial ovarian cancer: evolution of management in the era of precision medicine. CA Cancer J Clin 2019; 69: 280-304
  • 42 Hoy SM. Talazoparib: first global approval. Drugs 2018; 78: 1939-1946
  • 43 Desai C, Pathak A, Limaye S. et al. A review on mechanisms of resistance to PARP inhibitors. Ind J Cancer 2022; 59: S119-S129
  • 44 Dedes KJ, Wilkerson PM, Wetterskog D. et al. Synthetic lethality of PARP inhibition in cancers lacking BRCA1 and BRCA2 mutations. Cell Cycle 2011; 10: 1192-1199
  • 45 Sun C, Fang Y, Labrie M. et al. Systems approach to rational combination therapy: PARP inhibitors. Biochem Soc Trans 2020; 48: 1101-1108
  • 46 Syed YY. Rucaparib: first global approval. Drugs 2017; 77: 585-592
  • 47 Curtin NJ, Szabo C. Poly (ADP-ribose) polymerase inhibition: past, present and future. Nat Rev Drug Discov 2020; 19: 711-736
  • 48 Patel PS, Algouneh A, Hakem R. Exploiting synthetic lethality to target BRCA1/2-deficient tumors: where we stand. Oncogene 2021; 40: 3001-3014
  • 49 Coleman RL, Sill MW, Bell-McGuinn K. et al. A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation—an NRG oncology/gynecologic oncology group study. Gynecol Oncol 2015; 137: 386-391
  • 50 Boraei AT, Singh PK, Sechi M. et al. Discovery of novel functionalized 1, 2, 4-triazoles as PARP-1 inhibitors in breast cancer: Design, synthesis and antitumor activity evaluation. Eur J Med Chem 2019; 182: 111621
  • 51 Hu X, Zhang J, Zhang Y. et al. Dual-target inhibitors of poly (ADP-ribose) polymerase-1 for cancer therapy: Advances, challenges, and opportunities. Eur J Med Chem 2022; 230: 114094
  • 52 Wang J, Wang X, Li H. et al. Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors. Bioorganic Med Chem Lett 2016; 26: 4127-4132
  • 53 Scarpelli R, Boueres JK, Cerretani M. et al. Synthesis and biological evaluation of substituted 2-phenyl-2H-indazole-7-carboxamides as potent poly (ADP-ribose) polymerase (PARP) inhibitors. Bioorganic Med Chem Lett 2010; 20: 488-492
  • 54 Galindo-Campos MA, Bedora-Faure M, Farrés J. et al. Coordinated signals from the DNA repair enzymes PARP-1 and PARP-2 promotes B-cell development and function. Cell Death Differ 2019; 26: 2667-2681
  • 55 Mao K, Zhang G. The role of PARP1 in neurodegenerative diseases and aging. FEBS J 2022; 289: 2013-2024
  • 56 McSweeney M, Binette AP, Meyer PF. et al. Intermediate flortaucipir uptake is associated with Aβ-PET and CSF tau in asymptomatic adults. Neurol 2020; 94: e1190-e1200
  • 57 Kam TI, Mao X, Park H. et al. Poly (ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease. Sci 2018; 362: eaat8407
  • 58 Fang EF, Kassahun H, Croteau DL. et al. NAD+ replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair. Cell Metabol 2016; 24: 566-581
  • 59 Rulten SL, Rotheray A, Green RL. et al. PARP-1 dependent recruitment of the amyotrophic lateral sclerosis-associated protein FUS/TLS to sites of oxidative DNA damage. Nucleic Acids Res 2014; 42: 307-314
  • 60 Wang H, Guo W, Mitra J. et al. Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in Amyotrophic Lateral Sclerosis. Nat Commun 2018; 9: 3683
  • 61 Farez MF, Quintana FJ, Gandhi R. et al. Toll-like receptor 2 and poly (ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE. Nat Immunol 2009; 10: 958-964
  • 62 Horvath I, Weise CF, Andersson EK. et al. Mechanisms of protein oligomerization: inhibitor of functional amyloids templates α-synuclein fibrillation. J Am Chem Soc 2012; 134: 3439-3444
  • 63 Kim TW, Cho HM, Choi SY. et al. (ADP-ribose) polymerase 1 and AMP-activated protein kinase mediate progressive dopaminergic neuronal degeneration in a mouse model of Parkinson’s disease. Cell Death Dis 2013; 4: e919-e919
  • 64 Kim H, Ham S, Lee JY. et al. Estrogen receptor activation contributes to RNF146 expression and neuroprotection in Parkinson's disease models. Oncotarget 2017; 8: 106721
  • 65 Takahashi M, Kitaura H, Kakita A. et al. USP10 is a driver of ubiquitinated protein aggregation and aggresome formation to inhibit apoptosis. IScience 2018; 9: 433-450
  • 66 Zhou Z, Sun B, Huang S. et al. Roles of aminoacyl-tRNA synthetase-interacting multi-functional proteins in physiology and cancer. Cell Death Dis 2020; 11: 579
  • 67 Mao K, Chen J, Yu H. et al. Poly (ADP-ribose) polymerase 1 inhibition prevents neurodegeneration and promotes α-synuclein degradation via transcription factor EB-dependent autophagy in mutant α-synucleinA53T model of Parkinson's disease. Aging Cell 2020; 19: e13163
  • 68 Espinoza-Derout J, Shao XM, Bankole E. et al. Hepatic DNA damage induced by electronic cigarette exposure is associated with the modulation of NAD+/PARP1/SIRT1 axis. Front Endocrinol 2019; 10: 320
  • 69 Yu C, Kim B-S, Kim E. FAF1 mediates regulated necrosis through PARP1 activation upon oxidative stress leading to dopaminergic neurodegeneration. Cell Death Differ 2016; 23: 1873-1885
  • 70 Yun SP, Kim H, Ham S. et al. VPS35 regulates parkin substrate AIMP2 toxicity by facilitating lysosomal clearance of AIMP2. Cell Death Dis 2017; 8: e2741-e2741
  • 71 Tyagi N, Vacek JC, Givvimani S. et al. Cardiac specific deletion of N-methyl-d-aspartate receptor 1 ameliorates mtMMP-9 mediated autophagy/mitophagy in hyperhomocysteinemia. J Recept Signal Transduct 2010; 30: 78-87
  • 72 Zanon A, Pramstaller PP, Hicks AA. et al. Environmental and genetic variables influencing mitochondrial health and Parkinson’s disease penetrance. Parkinson’s Dis 2018; 2018
  • 73 Lin S, Wang Y, Zhang X. et al. HSP27 alleviates cardiac aging in mice via a mechanism involving antioxidation and mitophagy activation. Oxid Med Cell Longev 2016; 2016
  • 74 Fu W, Liu Y, Yin H. Mitochondrial dynamics: biogenesis, fission, fusion, and mitophagy in the regulation of stem cell behaviors. Stem Cells Int 2019; 2019
  • 75 Liu T, Yang Q, Zhang X. et al. Quercetin alleviates kidney fibrosis by reducing renal tubular epithelial cell senescence through the SIRT1/PINK1/mitophagy axis. Life Sci 2020; 257: 118116
  • 76 Szczesny B, Brunyanszki A, Olah G. et al. Opposing roles of mitochondrial and nuclear PARP1 in the regulation of mitochondrial and nuclear DNA integrity: implications for the regulation of mitochondrial function. Nucleic Acids Res 2014; 42: 13161-13173
  • 77 Wang Y, Lv D, Liu W. et al. Disruption of the circadian clock alters antioxidative defense via the SIRT1-BMAL1 pathway in 6-OHDA-induced models of Parkinson’s disease. Oxid Med Cellr Longev 2018; 2018
  • 78 Yang Z, Li L, Chen L. et al. PARP-1 mediates LPS-induced HMGB1 release by macrophages through regulation of HMGB1 acetylation. J Immunol 2014; 193: 6114-6123
  • 79 Sasaki T, Liu K, Agari T. et al. Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson's disease. Exp Neurol 2016; 275: 220-231
  • 80 He Y, She H, Zhang T. et al. p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by phosphorylating ULK1. J Cell Biol 2018; 217: 315-328
  • 81 Imbriani P, Schirinzi T, Meringolo M. et al. Centrality of early synaptopathy in Parkinson’s disease. Front Neurol 2018; 9: 103
  • 82 Morra JH, Tu Z, Apostolova LG. et al. Automated mapping of hippocampal atrophy in 1-year repeat MRI data from 490 subjects with Alzheimer's disease, mild cognitive impairment, and elderly controls. Neuroimage 2009; 45: S3-S15
  • 83 Madsen SK, Ho AJ, Hua X. et al. 3D maps localize caudate nucleus atrophy in 400 Alzheimer’s disease, mild cognitive impairment, and healthy elderly subjects. Neurobiol Aging 2010; 31: 1312-1325
  • 84 Bagyinszky E, Giau VV, An SA. Transcriptomics in Alzheimer’s disease: Aspects and challenges. Int J Mol Sci 2020; 21: 3517
  • 85 Narne P, Pandey V, Simhadri PK. et al. Poly (ADP-ribose) polymerase-1 hyperactivation in neurodegenerative diseases: The death knell tolls for neurons. Semin Cell Dev Biol 2017; 63: 154-166
  • 86 Toro CA, Zhang L, Cao J. et al. Sex differences in Alzheimer’s disease: Understanding the molecular impact. Brain Res 2019; 1719: 194-207
  • 87 Martire S, Mosca L, d’Erme M. PARP-1 involvement in neurodegeneration: a focus on Alzheimer’s and Parkinson’s diseases. Mech Ageing Dev 2015; 146: 53-64
  • 88 Nho K, Corneveaux JJ, Kim S. et al. Whole-exome sequencing and imaging genetics identify functional variants for rate of change in hippocampal volume in mild cognitive impairment. Mol Psychiatry 2013; 18: 781-787
  • 89 Regier M, Liang J, Choi A. et al. Evidence for decreased nucleolar PARP-1 as an early marker of cognitive impairment. Neural Plast 2019; 2019
  • 90 Hou Y, Song H, Croteau DL. et al. Genome instability in Alzheimer disease. Mech Ageing Develop 2017; 161: 83-94
  • 91 Beurel E. Regulation by glycogen synthase kinase-3 of inflammation and T cells in CNS diseases. Front Mol Neurosci 2011; 4: 18
  • 92 Chiarugi A, Moskowitz MA. Poly (ADP-ribose) polymerase-1 activity promotes NF-κB-driven transcription and microglial activation: implication for neurodegenerative disorders. J Neurochem 2003; 85: 306-317
  • 93 Hu XM, Dong W, Cui ZW. et al. In silico identification of AChE and PARP-1 dual-targeted inhibitors of Alzheimer’s disease. J Molecular Model 2018; 24: 1-9
  • 94 Salech F, Ponce DP, SanMartín CD. et al. PARP-1 and p53 regulate the increased susceptibility to oxidative death of lymphocytes from MCI and AD patients. Front Aging Neurosci 2017; 9: 310
  • 95 Kauppinen TM, Suh SW, Higashi Y. et al. Poly (ADP-ribose) polymerase-1 modulates microglial responses to amyloid β. J Neuroinflammation 2011; 8: 1-17
  • 96 Stoica BA, Loane DJ, Zhao Z. et al. PARP-1 inhibition attenuates neuronal loss, microglia activation and neurological deficits after traumatic brain injury. J Neurotrauma 2014; 31: 758-772
  • 97 Venkataraman K, Khurana S, Tai T. Oxidative stress in aging-matters of the heart and mind. Int J Mol Sci 2013; 14: 17897-17925
  • 98 Bourassa MW, Ratan RR. The interplay between microRNAs and histone deacetylases in neurological diseases. Neurochem Int 2014; 77: 33-39
  • 99 Lin X, Kapoor A, Gu Y. et al. Contributions of DNA damage to Alzheimer’s disease. Int J Mol Sci 2020; 21: 1666
  • 100 Yanez M, Jhanji M, Murphy K. et al. Nicotinamide augments the anti-inflammatory properties of resveratrol through PARP1 activation. Sci Rep 2019; 9: 10219
  • 101 Wencel PL, Lukiw WJ, Strosznajder JB. et al. Inhibition of poly (ADP-ribose) polymerase-1 enhances gene expression of selected sirtuins and APP cleaving enzymes in amyloid beta cytotoxicity. Mol Neurobiol 2018; 55: 4612-4623
  • 102 Van De Haar HJ, Burgmans S, Jansen JF. et al. Blood-brain barrier leakage in patients with early Alzheimer disease. Radiol 2016; 281: 527-535
  • 103 Magaki S, Tang Z, Tung S. et al. The effects of cerebral amyloid angiopathy on integrity of the blood-brain barrier. Neurobiol Aging 2018; 70: 70-77
  • 104 Atkinson MA, Maclaren NK, Riley WJ. et al. Are insulin autoantibodies markers for insulin-dependent diabetes mellitus?. Diabetes 1986; 35: 894-898
  • 105 Wilson GL, Hartig PC, Patton NJ. et al. Mechanisms of nitrosourea-induced β-cell damage: activation of poly (ADP-ribose) synthetase and cellular distribution. Diabetes 1988; 37: 213-216
  • 106 Bolaffi JL, Rodd GG, Wang JI. et al. Interrelationship of changes in islet nicotine adeninedinucleotide, insulin secretion, and cell viability induced by interleukin-1 beta. Endocrinol 1994; 134: 537-542
  • 107 Sandler S, Welsh M, Andersson A. Streptozotocin-induced impairment of islet B-cell metabolism and its prevention by a hydroxyl radical scavenger and inhibitors of poly (ADP-ribose) synthetase. Acta Pharmacol Toxicol 1983; 53: 392-400
  • 108 de La Lastra CA, Villegas I, Sanchez-Fidalgo S. Poly (ADP-ribose) polymerase inhibitors: new pharmacological functions and potential clinical implications. Curr Pharm Des 2007; 13: 933-962
  • 109 Gonzalez C, Ménissier de Murcia J, Janiak P. et al. Unexpected sensitivity of nonobese diabetic mice with a disrupted poly (ADP-Ribose) polymerase-1 gene to streptozotocin-induced and spontaneous diabetes. Diabetes 2002; 51: 1470-1476
  • 110 Vidal J, Fernandez-Balsells M, Sesmilo G. et al. Effects of nicotinamide and intravenous insulin therapy in newly diagnosed type 1 diabetes. Diabetes Care 2000; 23: 360-364
  • 111 Szabo C, Biser A, Benko R. et al. Poly (ADP-ribose) polymerase inhibitors ameliorate nephropathy of type 2 diabetic Lepr db/db mice. Diabetes 2006; 55: 3004-3012
  • 112 Li F, Szabo C, Pacher P. et al. Evaluation of orally active poly (ADP-ribose) polymerase inhibitor in streptozotocin-diabetic rat model of early peripheral neuropathy. Diabetologia 2004; 47: 710-717
  • 113 Ha HC, Juluri K, Zhou Y. et al. Poly (ADP-ribose) polymerase-1 is required for efficient HIV-1 integration. Proc Natl Acad Sci 2001; 98: 3364-3368
  • 114 Ariumi Y, Turelli P, Masutani M. et al. DNA damage sensors ATM, ATR, DNA-PKcs, and PARP-1 are dispensable for human immunodeficiency virus type 1 integration. J Virol 2005; 79: 2973-2978
  • 115 Kameoka M, Nukuzuma S, Itaya A. et al. RNA interference directed against Poly (ADP-Ribose) polymerase 1 efficiently suppresses human immunodeficiency virus type 1 replication in human cells. J Virol 2004; 78: 8931-8934
  • 116 Cole GA, Bauer G, Kirsten E. et al. Inhibition of HIV-1 IIIb replication in AA-2 and NT-2 cells in culture by two ligands of poly (ADP-ribose) polymerase: 6-amino-1, 2-benzopyrone and 5-iodo-6-amino-1, 2-benzopyrone. Biochem Biophys Res Commun 1991; 180: 504-514
  • 117 Yamagoe S, Kohda T, Oishi M. Poly (ADP-ribose) polymerase inhibitors suppress UV-induced human immunodeficiency virus type 1 gene expression at the posttranscriptional level. Mol Cell Biol 1991; 11: 3522-3527
  • 118 Kameoka M, Nukuzuma S, Itaya A. et al. Poly (ADP-ribose) polymerase-1 is required for integration of the human immunodeficiency virus type 1 genome near centromeric alphoid DNA in human and murine cells. Biochem Biophys Res Commun 2005; 334: 412-417
  • 119 Qian M, Liu Z, Peng L. et al. Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria. Elife 2018; 7: e34836
  • 120 Zha S, Li Z, Cao Q. et al. PARP1 inhibitor (PJ34) improves the function of aging-induced endothelial progenitor cells by preserving intracellular NAD+ levels and increasing SIRT1 activity. Stem Cell Res Ther 2018; 9: 1-10
  • 121 Martens CR, Denman BA, Mazzo MR. et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun 2018; 9: 1286
  • 122 Katsuumi G, Shimizu I, Yoshida Y. et al. Vascular senescence in cardiovascular and metabolic diseases. Front Cardiovasc Med 2018; 5: 18
  • 123 Meng Q, Guo T, Li G. et al. Dietary resveratrol improves antioxidant status of sows and piglets and regulates antioxidant gene expression in placenta by Keap1-Nrf2 pathway and Sirt1. J Anim Sci Biotechnol 2018; 9: 1-13