{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:16:45Z","timestamp":1791832605142,"version":"4.3.4"},"reference-count":192,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T00:00:00Z","timestamp":1622851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011909","name":"Charitable Trust Fund for Ophthalmic Research in Commemoration of Santen Pharmaceutical's Founder","doi-asserted-by":"publisher","award":["180742"],"award-info":[{"award-number":["180742"]}],"id":[{"id":"10.13039\/501100011909","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Glaucoma is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with age and the level of intraocular pressure (IOP). IOP reduction is currently the only therapeutic modality shown to slow glaucoma progression. However, patients still lose vision despite best treatment, suggesting that other factors confer susceptibility. Several studies indicate that mitochondrial function may underlie both susceptibility and resistance to developing glaucoma. Mitochondria meet high energy demand, in the form of ATP, that is required for the maintenance of optimum retinal ganglion cell (RGC) function. Reduced nicotinamide adenine dinucleotide (NAD+) levels have been closely correlated to mitochondrial dysfunction and have been implicated in several neurodegenerative diseases including glaucoma. NAD+ is at the centre of various metabolic reactions culminating in ATP production\u2014essential for RGC function. In this review we present various pathways that influence the NAD+(H) redox state, affecting mitochondrial function and making RGCs susceptible to degeneration. Such disruptions of the NAD+(H) redox state are generalised and not solely induced in RGCs because of high IOP. This places the NAD+(H) redox state as a potential systemic biomarker for glaucoma susceptibility and progression; a hypothesis which may be tested in clinical trials and then translated to clinical practice.<\/jats:p>","DOI":"10.3390\/cells10061402","type":"journal-article","created":{"date-parts":[[2021,6,6]],"date-time":"2021-06-06T23:59:55Z","timestamp":1623023995000},"page":"1402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Neuroprotection in Glaucoma: NAD+\/NADH Redox State as a Potential Biomarker and Therapeutic Target"],"prefix":"10.3390","volume":"10","author":[{"given":"Bledi","family":"Petriti","sequence":"first","affiliation":[{"name":"NIHR Biomedical Research Centre, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London EC1V 9EL, UK"},{"name":"Department of Clinical & Movement Neurosciences, UCL Queens Square Institute of Neurology, London NW3 2PF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-8397","authenticated-orcid":false,"given":"Pete A.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 171 64 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerassimos","family":"Lascaratos","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital NHS Foundation Trust, London and King\u2019s College London, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5797-2922","authenticated-orcid":false,"given":"Kai-Yin","family":"Chau","sequence":"additional","affiliation":[{"name":"Department of Clinical & Movement Neurosciences, UCL Queens Square Institute of Neurology, London NW3 2PF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2907-6992","authenticated-orcid":false,"given":"David F.","family":"Garway-Heath","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"f3518","DOI":"10.1136\/bmj.f3518","article-title":"Glaucoma","volume":"346","author":"King","year":"2013","journal-title":"BMJ Br. Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1176\/appi.neuropsych.12020030","article-title":"Depression, Anxiety, and Disturbed Sleep in Glaucoma","volume":"25","author":"Agorastos","year":"2013","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11910-018-0829-3","article-title":"Mitochondrial Dysfunction in Parkinson\u2019s Disease: New Mechanistic Insights and Therapeutic Perspectives","volume":"18","author":"Park","year":"2018","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.3233\/JAD-170585","article-title":"Mitochondria and Mitochondrial Cascades in Alzheimer\u2019s Disease","volume":"62","author":"Swerdlow","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Yepez, V.A., Kremer, L.S., Iuso, A., Gusic, M., Kopajtich, R., Konarikova, E., Nadel, A., Wachutka, L., Prokisch, H., and Gagneur, J. (2018). OCR-Stats: Robust estimation and statistical testing of mitochondrial respiration activities using Seahorse XF Analyzer. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199938"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.cmet.2019.09.001","article-title":"NAD(+) in Brain Aging and Neurodegenerative Disorders","volume":"30","author":"Lautrup","year":"2019","journal-title":"Cell Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/s41392-020-00311-7","article-title":"NAD+ metabolism: Pathophysiologic mechanisms and therapeutic potential","volume":"5","author":"Xie","year":"2020","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S0002-9394(01)00964-3","article-title":"Risk factors for progression of visual field abnormalities in normal-tension glaucoma","volume":"131","author":"Drance","year":"2001","journal-title":"Am. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.ajo.2013.05.027","article-title":"Lifetime risk of blindness in open-angle glaucoma","volume":"156","author":"Peters","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s13167-017-0097-3","article-title":"Relationship between normal tension glaucoma and Flammer syndrome","volume":"8","author":"Konieczka","year":"2017","journal-title":"Epma J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.exer.2015.02.011","article-title":"Optic nerve head biomechanics in aging and disease","volume":"133","author":"Downs","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nature11707","article-title":"Mitochondrial disorders as windows into an ancient organelle","volume":"491","author":"Vafai","year":"2012","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Casson, R.J., Chidlow, G., Crowston, J.G., Williams, P.A., and Wood, J.P.M. (2020). Retinal energy metabolism in health and glaucoma. Prog. Retin. Eye Res., 100881.","DOI":"10.1016\/j.preteyeres.2020.100881"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1167\/iovs.02-0333","article-title":"Varicosities of intraretinal ganglion cell axons in human and nonhuman primates","volume":"44","author":"Wang","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.freeradbiomed.2012.05.009","article-title":"Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration","volume":"53","author":"Arenas","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Genc, S., Kurnaz, I.A., and Ozilgen, M. (2011). Astrocyte - neuron lactate shuttle may boost more ATP supply to the neuron under hypoxic conditions - in silico study supported by in vitro expression data. BMC Syst. Biol., 5.","DOI":"10.1186\/1752-0509-5-162"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/glia.21242","article-title":"Structural basis of glaucoma: The fortified astrocytes of the optic nerve head are the target of raised intraocular pressure","volume":"60","author":"Dai","year":"2012","journal-title":"Glia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S1350-9462(00)00027-6","article-title":"Oxygen Distribution and Consumption within the Retina in Vascularised and Avascular Retinas and in Animal Models of Retinal Disease","volume":"20","author":"Yu","year":"2001","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_20","first-page":"1009","article-title":"Normal Tension Glaucoma patients have reduced systemic mitochondrial function compared to High Tension Glaucoma patients [ARVO abstract]","volume":"61","author":"Petriti","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12640-009-9051-z","article-title":"Mechanism for quinolinic acid cytotoxicity in human astrocytes and neurons","volume":"16","author":"Braidy","year":"2009","journal-title":"Neurotox. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/jnc.12325","article-title":"Critical role of Nrf2 in oxidative stress-induced retinal ganglion cell death","volume":"127","author":"Himori","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.bbrc.2014.08.009","article-title":"The role of calpain in an in vivo model of oxidative stress-induced retinal ganglion cell damage","volume":"451","author":"Yokoyama","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1126\/science.aad4017","article-title":"Complementation of mitochondrial electron transport chain by manipulation of the NAD+\/NADH ratio","volume":"352","author":"Titov","year":"2016","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.cell.2013.11.037","article-title":"Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging","volume":"155","author":"Gomes","year":"2013","journal-title":"Cell"},{"key":"ref_26","first-page":"120","article-title":"Elevated hydrostatic pressure triggers release of OPA1 and cytochrome C, and induces apoptotic cell death in differentiated RGC-5 cells","volume":"15","author":"Ju","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s00439-001-0645-7","article-title":"A major marker for normal tension glaucoma: Association with polymorphisms in the OPA1 gene","volume":"110","author":"Aung","year":"2002","journal-title":"Hum. Genet."},{"key":"ref_28","first-page":"460","article-title":"Polymorphisms in OPA1 are associated with normal tension glaucoma","volume":"9","author":"Powell","year":"2003","journal-title":"Mol. Vis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1136\/jmg.2009.067512","article-title":"OPA1 increases the risk of normal but not high tension glaucoma","volume":"47","author":"Stewart","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ajo.2006.09.028","article-title":"The OPA1 gene polymorphism is associated with normal tension and high tension glaucoma","volume":"143","author":"Mabuchi","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1167\/iovs.05-1639","article-title":"Mitochondrial abnormalities in patients with primary open-angle glaucoma","volume":"47","author":"Morales","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Van Bergen, N.J., Crowston, J.G., Craig, J.E., Burdon, K.P., Kearns, L.S., Sharma, S., Hewitt, A.W., Mackey, D.A., and Trounce, I.A. (2015). Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140919"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1167\/iovs.12-9596","article-title":"Impaired complex-I-linked respiration and ATP synthesis in primary open-angle glaucoma patient lymphoblasts","volume":"53","author":"Lee","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wolf, C., Gramer, E., Muller-Myhsok, B., Pasutto, F., Reinthal, E., Wissinger, B., and Weisschuh, N. (2009). Evaluation of nine candidate genes in patients with normal tension glaucoma: A case control study. BMC Med. Genet., 10.","DOI":"10.1186\/1471-2350-10-91"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3389\/fnmol.2018.00350","article-title":"Overexpression of Optic Atrophy Type 1 Protects Retinal Ganglion Cells and Upregulates Parkin Expression in Experimental Glaucoma","volume":"11","author":"Hu","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5046","DOI":"10.1167\/iovs.16-20017","article-title":"Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses","volume":"57","author":"Khawaja","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ng.3482","article-title":"Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma","volume":"48","author":"Bailey","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/s41588-018-0126-8","article-title":"Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma","volume":"50","author":"Khawaja","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/gim.2014.121","article-title":"Whole-mitochondrial genome sequencing in primary open-angle glaucoma using massively parallel sequencing identifies novel and known pathogenic variants","volume":"17","author":"Sundaresan","year":"2015","journal-title":"Genet. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.nbd.2015.05.012","article-title":"Resistance to the most common optic neuropathy is associated with systemic mitochondrial efficiency","volume":"82","author":"Lascaratos","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1126\/science.aal0092","article-title":"Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice","volume":"355","author":"Williams","year":"2017","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1089\/jop.2011.0062","article-title":"Plasma citrate levels as a potential biomarker for glaucoma","volume":"27","author":"Fraenkl","year":"2011","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_43","first-page":"2669","article-title":"Plasma Citrate Levels as a Biomarker for Glaucoma Diagnosis","volume":"51","author":"Goldblum","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/S0002-9394(03)00788-8","article-title":"Oxidative stress markers in aqueous humor of glaucoma patients","volume":"137","author":"Ferreira","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/S0002-9343(03)00114-1","article-title":"Oxidative deoxyribonucleic acid damage in the eyes of glaucoma patients","volume":"114","author":"Izzotti","year":"2003","journal-title":"Am. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1001\/archopht.123.4.458","article-title":"Oxidative DNA damage in the human trabecular meshwork: Clinical correlation in patients with primary open-angle glaucoma","volume":"123","author":"Pascotto","year":"2005","journal-title":"Arch. Ophthalmol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1167\/iovs.04-0777","article-title":"Systemic reduction in glutathione levels occurs in patients with primary open-angle glaucoma","volume":"46","author":"Gherghel","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/sj.eye.6701565","article-title":"Role of oxidative stress enzymes in open-angle glaucoma","volume":"19","author":"Yildirim","year":"2005","journal-title":"Eye (Lond.)"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e49680","DOI":"10.1371\/journal.pone.0049680","article-title":"Status of systemic oxidative stresses in patients with primary open-angle glaucoma and pseudoexfoliation syndrome","volume":"7","author":"Tanito","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_50","first-page":"41","article-title":"Oxidative DNA damage and total antioxidant status in glaucoma patients","volume":"17","author":"Sorkhabi","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e259","DOI":"10.1111\/j.1755-3768.2010.01997.x","article-title":"Increased serum total antioxidant status and decreased urinary 8-hydroxy-2\u2019-deoxyguanosine levels in patients with normal-tension glaucoma","volume":"88","author":"Yuki","year":"2010","journal-title":"Acta Ophthalmol"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"18426","DOI":"10.1074\/jbc.M301295200","article-title":"Intra-mitochondrial poly(ADP-ribosylation) contributes to NAD+ depletion and cell death induced by oxidative stress","volume":"278","author":"Du","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/S0039-9140(02)00125-X","article-title":"Flow injection analysis of trace amounts of NADH with inhibited chemiluminescent detection","volume":"57","author":"Li","year":"2002","journal-title":"Talanta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/BF03033501","article-title":"Promotion of cellular NAD(+) anabolism: Therapeutic potential for oxidative stress in ageing and Alzheimer\u2019s disease","volume":"13","author":"Braidy","year":"2008","journal-title":"Neurotox. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00018-003-3161-1","article-title":"Enzymology of NAD+ homeostasis in man","volume":"61","author":"Magni","year":"2004","journal-title":"Cell. Mol. Life Sci. Cmls"},{"key":"ref_56","first-page":"135","article-title":"Enzymology of NAD+ synthesis","volume":"73","author":"Magni","year":"1999","journal-title":"Adv. Enzymol. Relat. Areas Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"77","DOI":"10.4161\/cam.3.1.7483","article-title":"NAD and axon degeneration: From the Wlds gene to neurochemistry","volume":"3","author":"Wang","year":"2009","journal-title":"Cell Adhes. Migr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.cmet.2020.02.001","article-title":"Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway","volume":"31","author":"Shats","year":"2020","journal-title":"Cell Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1210\/er.2009-0026","article-title":"The secret life of NAD+: An old metabolite controlling new metabolic signaling pathways","volume":"31","author":"Houtkooper","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1002\/jnr.22638","article-title":"The NAD+ \/NADH redox state in astrocytes: Independent control of the NAD+ and NADH content","volume":"89","author":"Wilhelm","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_61","unstructured":"Mathews, C.K., Van Holde, K.E., and Ahern, K.G. (2000). Biochemistry, Benjamin Cummings. [3rd ed.]."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1101\/gad.1164804","article-title":"Calorie restriction extends yeast life span by lowering the level of NADH","volume":"18","author":"Lin","year":"2004","journal-title":"Genes Dev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0955-0674(03)00006-1","article-title":"Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease","volume":"15","author":"Lin","year":"2003","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6161","DOI":"10.1074\/jbc.M607661200","article-title":"The dihydrolipoamide acetyltransferase is a novel metabolic longevity factor and is required for calorie restriction-mediated life span extension","volume":"282","author":"Easlon","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1046\/j.1471-4159.1996.67031259.x","article-title":"Shift of the cellular oxidation-reduction potential in neural cells expressing Bcl-2","volume":"67","author":"Ellerby","year":"1996","journal-title":"J. Neurochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1126\/science.1069300","article-title":"Regulation of Corepressor Function by Nuclear NADH","volume":"295","author":"Zhang","year":"2002","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.mce.2016.11.003","article-title":"NAD and the aging process: Role in life, death and everything in between","volume":"455","author":"Chini","year":"2017","journal-title":"Mol Cell Endocrinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/nrm.2016.14","article-title":"Nuclear DNA damage signalling to mitochondria in ageing","volume":"17","author":"Fang","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1080\/15548627.2019.1596497","article-title":"Mitophagy and NAD(+) inhibit Alzheimer disease","volume":"15","author":"Fang","year":"2019","journal-title":"Autophagy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1016\/j.celrep.2018.05.009","article-title":"The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson\u2019s Disease","volume":"23","author":"Ivanyuk","year":"2018","journal-title":"Cell Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cmet.2019.05.015","article-title":"Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice","volume":"30","author":"Yoshida","year":"2019","journal-title":"Cell Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1002\/jnr.21650","article-title":"High doses of nicotinamide prevent oxidative mitochondrial dysfunction in a cellular model and improve motor deficit in a Drosophila model of Parkinson\u2019s disease","volume":"86","author":"Jia","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_73","first-page":"141","article-title":"Enhancing NAD(+) salvage metabolism is neuroprotective in a PINK1 model of Parkinson\u2019s disease","volume":"6","author":"Lehmann","year":"2017","journal-title":"Biol. Open"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e2166","DOI":"10.1038\/cddis.2016.72","article-title":"Parp mutations protect against mitochondrial dysfunction and neurodegeneration in a PARKIN model of Parkinson\u2019s disease","volume":"7","author":"Lehmann","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1167\/iovs.19-27099","article-title":"Nicotinamide Deficiency in Primary Open-Angle Glaucoma","volume":"60","author":"Guehlouz","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_76","first-page":"3493","article-title":"Improvement in inner retinal function in glaucoma in response to nicotinamide (Vitamin B3) supplementation: A crossover randomized clinical trial","volume":"61","author":"Hui","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Gilley, J., and Coleman, M.P. (2010). Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000300"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.cmet.2018.03.018","article-title":"Quantitative Analysis of NAD Synthesis-Breakdown Fluxes","volume":"27","author":"Liu","year":"2018","journal-title":"Cell Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1083\/jcb.200504028","article-title":"A local mechanism mediates NAD-dependent protection of axon degeneration","volume":"170","author":"Wang","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s11306-019-1604-4","article-title":"Diverse therapeutic efficacies and more diverse mechanisms of nicotinamide","volume":"15","author":"Song","year":"2019","journal-title":"Metabolomics"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Nikas, I.P., Paschou, S.A., and Ryu, H.S. (2020). The Role of Nicotinamide in Cancer Chemoprevention and Therapy. Biomolecules, 10.","DOI":"10.3390\/biom10030477"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1089\/ars.2018.7722","article-title":"Cellular Compartmentation and the Redox\/Nonredox Functions of NAD","volume":"31","author":"Kulkarni","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.cell.2007.07.035","article-title":"Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival","volume":"130","author":"Yang","year":"2007","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"410","DOI":"10.2741\/3252","article-title":"The NMN\/NaMN adenylyltransferase (NMNAT) protein family","volume":"14","author":"Lau","year":"2009","journal-title":"Front Biosci (Landmark Ed.)"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e19749","DOI":"10.7554\/eLife.19749","article-title":"NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD(+) depletion","volume":"5","author":"Sasaki","year":"2016","journal-title":"eLife"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nature06721","article-title":"NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration","volume":"452","author":"Zhai","year":"2008","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1126\/science.1098014","article-title":"Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration","volume":"305","author":"Araki","year":"2004","journal-title":"Science"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1083\/jcb.200807175","article-title":"Wld S protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice","volume":"184","author":"Conforti","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1038\/ng.2361","article-title":"NMNAT1 mutations cause Leber congenital amaurosis","volume":"44","author":"Falk","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/ng.2356","article-title":"Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration","volume":"44","author":"Koenekoop","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.omtm.2020.07.003","article-title":"Gene Therapy Preserves Retinal Structure and Function in a Mouse Model of NMNAT1-Associated Retinal Degeneration","volume":"18","author":"Greenwald","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Milde, S., Gilley, J., and Coleman, M.P. (2013). Subcellular localization determines the stability and axon protective capacity of axon survival factor Nmnat2. PLoS Biol., 11.","DOI":"10.1371\/journal.pbio.1001539"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Fulleylove-Krause, B.K., Sison, S.L., and Ebert, A.D. (2020). Nicotinamide mononucleotide treatment increases NAD+ levels in an iPSC Model of Parkinson\u2019s Disease. bioRxiv.","DOI":"10.1101\/2020.05.06.080911"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1126\/science.1068613","article-title":"Axonal self-destruction and neurodegeneration","volume":"296","author":"Raff","year":"2002","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1460-9568.1989.tb00771.x","article-title":"Absence of Wallerian Degeneration does not Hinder Regeneration in Peripheral Nerve","volume":"1","author":"Lunn","year":"1989","journal-title":"Eur. J. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1083\/jcb.200706181","article-title":"Axons of retinal ganglion cells are insulted in the optic nerve early in DBA\/2J glaucoma","volume":"179","author":"Howell","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1111\/j.1460-9568.2008.06426.x","article-title":"The WldS gene delays axonal but not somatic degeneration in a rat glaucoma model","volume":"28","author":"Beirowski","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1167\/iovs.12-10861","article-title":"Protection of mouse retinal ganglion cell axons and soma from glaucomatous and ischemic injury by cytoplasmic overexpression of Nmnat1","volume":"54","author":"Zhu","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nrn3680","article-title":"Wallerian degeneration: An emerging axon death pathway linking injury and disease","volume":"15","author":"Conforti","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/nn770","article-title":"Wallerian degeneration of injured axons and synapses is delayed by a Ube4b\/Nmnat chimeric gene","volume":"4","author":"Mack","year":"2001","journal-title":"Nat. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1083\/jcb.200808042","article-title":"Wld S requires Nmnat1 enzymatic activity and N16-VCP interactions to suppress Wallerian degeneration","volume":"184","author":"Avery","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1091\/mbc.e05-04-0375","article-title":"The slow Wallerian degeneration protein, WldS, binds directly to VCP\/p97 and partially redistributes it within the nucleus","volume":"17","author":"Laser","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e860","DOI":"10.1038\/cddis.2013.391","article-title":"Axonal protection by Nmnat3 overexpression with involvement of autophagy in optic nerve degeneration","volume":"4","author":"Kitaoka","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1073\/pnas.84.10.3491","article-title":"Quinolinic acid phosphoribosyltransferase: Preferential glial localization in the rat brain visualized by immunocytochemistry","volume":"84","author":"Okuno","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41590-018-0255-3","article-title":"Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation","volume":"20","author":"Minhas","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1179\/135100002125000550","article-title":"Implications of the kynurenine pathway and quinolinic acid in Alzheimer\u2019s disease","volume":"7","author":"Guillemin","year":"2002","journal-title":"Redox Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0306-4522(93)90380-X","article-title":"Molecular profile of reactive astrocytes--implications for their role in neurologic disease","volume":"54","author":"Eddleston","year":"1993","journal-title":"Neuroscience"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1001\/archopht.1997.01100150499009","article-title":"Nitric oxide synthase in the human glaucomatous optic nerve head","volume":"115","author":"Neufeld","year":"1997","journal-title":"Arch. Ophthalmol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/eye.2000.128","article-title":"Optic nerve head structure in glaucoma: Astrocytes as mediators of axonal damage","volume":"14","author":"Morgan","year":"2000","journal-title":"Eye"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Fiedorowicz, M., Choragiewicz, T., Turski, W.A., Kocki, T., Nowakowska, D., Wertejuk, K., Kami\u0144ska, A., Avitabile, T., We\u0142niak-Kaminska, M., and Grieb, P. (2021). Tryptophan Pathway Abnormalities in a Murine Model of Hereditary Glaucoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031039"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"8538","DOI":"10.1007\/s12035-018-1003-2","article-title":"Kynurenic Acid Restores Nrf2 Levels and Prevents Quinolinic Acid-Induced Toxicity in Rat Striatal Slices","volume":"55","author":"Ferreira","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0042-6989(02)00682-X","article-title":"Alterations of kynurenic acid content in the retina in response to retinal ganglion cell damage","volume":"43","author":"Rejdak","year":"2003","journal-title":"Vision Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/bies.20085","article-title":"The PARP superfamily","volume":"26","author":"Spenlehauer","year":"2004","journal-title":"Bioessays"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1111\/bph.12416","article-title":"Parthanatos: Mitochondrial-linked mechanisms and therapeutic opportunities","volume":"171","author":"Fatokun","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/sj.cdd.4400872","article-title":"Increased expression and activation of poly(ADP-ribose) polymerase (PARP) contribute to retinal ganglion cell death following rat optic nerve transection","volume":"8","author":"Weise","year":"2001","journal-title":"Cell Death Differ."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1093\/brain\/122.2.247","article-title":"Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer\u2019s disease","volume":"122","author":"Love","year":"1999","journal-title":"Brain"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"5774","DOI":"10.1073\/pnas.96.10.5774","article-title":"Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism","volume":"96","author":"Mandir","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.cmet.2016.09.004","article-title":"NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair","volume":"24","author":"Fang","year":"2016","journal-title":"Cell Metab."},{"key":"ref_119","first-page":"3630","article-title":"Cell Death Markers in Primary Open-Angle Glaucoma [ARVO abstract]","volume":"50","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Salech, F., Ponce, D.P., Paula-Lima, A.C., SanMartin, C.D., and Behrens, M.I. (2020). Nicotinamide, a Poly [ADP-Ribose] Polymerase 1 (PARP-1) Inhibitor, as an Adjunctive Therapy for the Treatment of Alzheimer\u2019s Disease. Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.00255"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1016\/j.bbrc.2006.05.042","article-title":"Regulation of intracellular levels of NAD: A novel role for CD38","volume":"345","author":"Aksoy","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1096\/fj.07-8290com","article-title":"The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity","volume":"21","author":"Barbosa","year":"2007","journal-title":"FASEB J."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nature05526","article-title":"CD38 is critical for social behaviour by regulating oxytocin secretion","volume":"446","author":"Jin","year":"2007","journal-title":"Nature"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0006-8993(95)00885-T","article-title":"Neuronal localization of CD38 antigen in the human brain","volume":"697","author":"Mizuguchi","year":"1995","journal-title":"Brain Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1046\/j.1471-4159.2001.00455.x","article-title":"Evidence of a role for cyclic ADP-ribose in calcium signalling and neurotransmitter release in cultured astrocytes","volume":"78","author":"Verderio","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"92","DOI":"10.4049\/jimmunol.181.1.92","article-title":"Dual role of CD38 in microglial activation and activation-induced cell death","volume":"181","author":"Mayo","year":"2008","journal-title":"J. Immunol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.cmet.2016.05.006","article-title":"CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism","volume":"23","author":"Chini","year":"2016","journal-title":"Cell Metab."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1021\/pr4010597","article-title":"Overexpression of CD38 decreases cellular NAD levels and alters the expression of proteins involved in energy metabolism and antioxidant defense","volume":"13","author":"Hu","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10522-013-9489-5","article-title":"Mapping NAD(+) metabolism in the brain of ageing Wistar rats: Potential targets for influencing brain senescence","volume":"15","author":"Braidy","year":"2014","journal-title":"Biogerontology"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Guerreiro, S., Privat, A.-L., Bressac, L., and Toulorge, D. (2020). CD38 in Neurodegeneration and Neuroinflammation. Cells, 9.","DOI":"10.3390\/cells9020471"},{"key":"ref_131","first-page":"235","article-title":"BST-1\/CD157 regulates the humoral immune responses in vivo","volume":"75","author":"Ishihara","year":"2000","journal-title":"Chem. Immunol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/ng.485","article-title":"Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson\u2019s disease","volume":"41","author":"Satake","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1021\/acs.biochem.9b01078","article-title":"Initial Kinetic Characterization of Sterile Alpha and Toll\/Interleukin Receptor Motif-Containing Protein 1","volume":"59","author":"Loring","year":"2020","journal-title":"Biochemistry"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1126\/science.1258366","article-title":"SARM1 activation triggers axon degeneration locally via NAD\u207a destruction","volume":"348","author":"Gerdts","year":"2015","journal-title":"Science"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1016\/j.celrep.2015.11.032","article-title":"Wallerian Degeneration Is Executed by an NMN-SARM1-Dependent Late Ca(2+) Influx but Only Modestly Influenced by Mitochondria","volume":"13","author":"Loreto","year":"2015","journal-title":"Cell Rep."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Loreto, A., Hill, C.S., Hewitt, V.L., Orsomando, G., Angeletti, C., Gilley, J., Lucci, C., Sanchez-Martinez, A., Whitworth, A.J., and Conforti, L. (2019). Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration. bioRxiv.","DOI":"10.1101\/683342"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1084\/jem.20070868","article-title":"MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival","volume":"204","author":"Kim","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Ko, K.W., Milbrandt, J., and DiAntonio, A. (2020). SARM1 acts downstream of neuroinflammatory and necroptotic signaling to induce axon degeneration. J. Cell Biol., 219.","DOI":"10.1083\/jcb.201912047"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Ozaki, E., Gibbons, L., Neto, N.G., Kenna, P., Carty, M., Humphries, M., Humphries, P., Campbell, M., Monaghan, M., and Bowie, A. (2020). SARM1 deficiency promotes rod and cone photoreceptor cell survival in a model of retinal degeneration. Life Sci. Alliance, 3.","DOI":"10.26508\/lsa.201900618"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"107498","DOI":"10.1016\/j.celrep.2020.03.062","article-title":"Passenger Mutations Confound Phenotypes of SARM1-Deficient Mice","volume":"31","author":"Uccellini","year":"2020","journal-title":"Cell Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"9338","DOI":"10.1523\/JNEUROSCI.0877-14.2014","article-title":"Mitochondrial dysfunction induces Sarm1-dependent cell death in sensory neurons","volume":"34","author":"Summers","year":"2014","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1167\/iovs.12-10973","article-title":"Excitotoxicity upregulates SARM1 protein expression and promotes Wallerian-like degeneration of retinal ganglion cells and their axons","volume":"54","author":"Massoll","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.exer.2018.03.007","article-title":"Role of SARM1 and DR6 in retinal ganglion cell axonal and somal degeneration following axonal injury","volume":"171","author":"Fernandes","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1126\/science.1223899","article-title":"dSarm\/Sarm1 is required for activation of an injury-induced axon death pathway","volume":"337","author":"Osterloh","year":"2012","journal-title":"Science"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jchemneu.2017.11.009","article-title":"Mitochondrial SIRT3 and neurodegenerative brain disorders","volume":"95","author":"Khanna","year":"2019","journal-title":"J. Chem. Neuroanat."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cmet.2015.05.023","article-title":"NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus","volume":"22","author":"Menzies","year":"2015","journal-title":"Cell Metab."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0092-8674(01)00527-X","article-title":"hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase","volume":"107","author":"Vaziri","year":"2001","journal-title":"Cell"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0092-8674(01)00524-4","article-title":"Negative control of p53 by Sir2alpha promotes cell survival under stress","volume":"107","author":"Luo","year":"2001","journal-title":"Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/nrc2962","article-title":"SIRT1: Recent lessons from mouse models","volume":"10","author":"Herranz","year":"2010","journal-title":"Nature reviews. Cancer"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.cell.2006.11.013","article-title":"Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha","volume":"127","author":"Lagouge","year":"2006","journal-title":"Cell"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.cmet.2007.07.003","article-title":"SIRT2 regulates adipocyte differentiation through FoxO1 acetylation\/deacetylation","volume":"6","author":"Jing","year":"2007","journal-title":"Cell Metab."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S1097-2765(03)00038-8","article-title":"The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase","volume":"11","author":"North","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"8807","DOI":"10.1128\/MCB.01636-07","article-title":"Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation","volume":"27","author":"Lombard","year":"2007","journal-title":"Mol. Cell Biol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nature08778","article-title":"SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation","volume":"464","author":"Hirschey","year":"2010","journal-title":"Nature"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"14608","DOI":"10.1073\/pnas.1111308108","article-title":"Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production","volume":"108","author":"Jing","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.chembiol.2017.06.002","article-title":"SIRT4 Is a Regulator of Insulin Secretion","volume":"24","author":"Zaganjor","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"31995","DOI":"10.1074\/jbc.M110.124164","article-title":"SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells","volume":"285","author":"Nasrin","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e12789","DOI":"10.1111\/acel.12789","article-title":"SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation","volume":"17","author":"Zeng","year":"2018","journal-title":"Aging Cell"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.cell.2009.02.026","article-title":"SIRT5 Deacetylates Carbamoyl Phosphate Synthetase 1 and Regulates the Urea Cycle","volume":"137","author":"Nakagawa","year":"2009","journal-title":"Cell"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"10239","DOI":"10.1074\/jbc.M117.785022","article-title":"Lysine desuccinylase SIRT5 binds to cardiolipin and regulates the electron transport chain","volume":"292","author":"Zhang","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.molcel.2015.05.022","article-title":"SIRT5 Regulates both Cytosolic and Mitochondrial Protein Malonylation with Glycolysis as a Major Target","volume":"59","author":"Nishida","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.cell.2005.11.044","article-title":"Genomic instability and aging-like phenotype in the absence of mammalian SIRT6","volume":"124","author":"Mostoslavsky","year":"2006","journal-title":"Cell"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.cell.2009.12.041","article-title":"The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha","volume":"140","author":"Zhong","year":"2010","journal-title":"Cell"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nature10815","article-title":"The sirtuin SIRT6 regulates lifespan in male mice","volume":"483","author":"Kanfi","year":"2012","journal-title":"Nature"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.15252\/embj.201593499","article-title":"SIRT7 promotes genome integrity and modulates non-homologous end joining DNA repair","volume":"35","author":"Vazquez","year":"2016","journal-title":"EMBO J."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1167\/iovs.13-12157","article-title":"SIRT1 Promotes RGC Survival and Delays Loss of Function Following Optic Nerve Crush","volume":"54","author":"Zuo","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.tibs.2010.07.003","article-title":"Sirtuin regulation of mitochondria: Energy production, apoptosis, and signaling","volume":"35","author":"Verdin","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1167\/iovs.08-2817","article-title":"Sirt1 Involvement in rd10 Mouse Retinal Degeneration","volume":"50","author":"Jaliffa","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"6172","DOI":"10.3390\/s100606172","article-title":"SirT1--A sensor for monitoring self-renewal and aging process in retinal stem cells","volume":"10","author":"Peng","year":"2010","journal-title":"Sensors (Basel)"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.exer.2013.07.017","article-title":"The role of SIRT1 in ocular aging","volume":"116","author":"Mimura","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_171","first-page":"2398","article-title":"Up-regulation of sirtuins in the glaucomatous human retina","volume":"55","author":"Yang","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.1167\/iovs.11-9259","article-title":"Evaluation of Sirtuin Role in Neuroprotection of Retinal Ganglion Cells in Hypoxia","volume":"53","author":"Balaiya","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1089\/ars.2019.7803","article-title":"Metabolic Responses to Reductive Stress","volume":"32","author":"Xiao","year":"2020","journal-title":"Antioxid. Redox Signal."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1016\/S0021-9258(19)69779-6","article-title":"NADH inhibition and NAD activation of Escherichia coli lipoamide dehydrogenase catalyzing the NADH-lipoamide reaction","volume":"256","author":"Wilkinson","year":"1981","journal-title":"J. Biol. Chem."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1161\/CIRCRESAHA.111.246371","article-title":"Pyridine nucleotide regulation of cardiac intermediary metabolism","volume":"111","author":"Ussher","year":"2012","journal-title":"Circ. Res."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Sharma, R., Reinstadler, B., Engelstad, K., Skinner, O.S., Stackowitz, E., Haller, R.G., Clish, C.B., Pierce, K., Walker, M.A., and Fryer, R. (2021). Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity. J. Clin. Investig., 131.","DOI":"10.1172\/JCI136055"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Annesley, S.J., and Fisher, P.R. (2021). Lymphoblastoid Cell Lines as Models to Study Mitochondrial Function in Neurological Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094536"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ajo.2004.04.058","article-title":"An evidence-based assessment of risk factors for the progression of ocular hypertension and glaucoma","volume":"138","author":"Friedman","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"iii","DOI":"10.3310\/hta11410","article-title":"The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma: A systematic review and economic evaluation","volume":"11","author":"Burr","year":"2007","journal-title":"Health Technol. Assess."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Burr, J.M., Campbell, M.K., Campbell, S.E., Francis, J.J., Greene, A., Hern\u00e1ndez, R., Hopkins, D., McCann, S.K., and Vale, L.D. (2011). Developing the clinical components of a complex intervention for a glaucoma screening trial: A mixed methods study. BMC Med. Res. Methodol., 11.","DOI":"10.1186\/1471-2288-11-54"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1067\/mcp.2001.113989","article-title":"Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework","volume":"69","author":"Group","year":"2001","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.stemcr.2020.05.009","article-title":"Retinal Ganglion Cells With a Glaucoma OPTN(E50K) Mutation Exhibit Neurodegenerative Phenotypes when Derived from Three-Dimensional Retinal Organoids","volume":"15","author":"VanderWall","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Alonso-Lavin, A.J., Baji\u0107, D., and Poyatos, J.F. (2019). Tolerance to NADH\/NAD+ imbalance anticipates aging and anti-aging interventions. bioRxiv.","DOI":"10.1101\/719401"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"17017","DOI":"10.1038\/sigtrans.2017.17","article-title":"Nicotinamide adenine dinucleotide replenishment rescues colon degeneration in aged mice","volume":"2","author":"Zhu","year":"2017","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"e19194","DOI":"10.1371\/journal.pone.0019194","article-title":"Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats","volume":"6","author":"Braidy","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.cmet.2015.11.011","article-title":"Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype","volume":"23","author":"Wiley","year":"2016","journal-title":"Cell Metab."},{"key":"ref_188","first-page":"145","article-title":"Sources and implications of NADH\/NAD(+) redox imbalance in diabetes and its complications","volume":"9","author":"Wu","year":"2016","journal-title":"DiabetesMetab. Syndr. Obes. Targets Ther."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Akie, T.E., Liu, L., Nam, M., Lei, S., and Cooper, M.P. (2015). OXPHOS-Mediated Induction of NAD+ Promotes Complete Oxidation of Fatty Acids and Interdicts Non-Alcoholic Fatty Liver Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125617"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.cmet.2013.07.002","article-title":"Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure","volume":"18","author":"Karamanlidis","year":"2013","journal-title":"Cell Metab."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1093\/hmg\/dds095","article-title":"Friedreich\u2019s ataxia reveals a mechanism for coordinate regulation of oxidative metabolism via feedback inhibition of the SIRT3 deacetylase","volume":"21","author":"Wagner","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Tribble, J.R., Otmani, A., Sun, S., Ellis, S.A., Cimaglia, G., Vohra, R., J\u00f6e, M., Lardner, E., Venkataraman, A.P., and Dom\u00ednguez-Vicent, A. (2020). Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction. bioRxiv.","DOI":"10.1101\/2020.10.21.348250"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/6\/1402\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:11:20Z","timestamp":1760163080000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/6\/1402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,5]]},"references-count":192,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["cells10061402"],"URL":"https:\/\/doi.org\/10.3390\/cells10061402","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,5]]}}}