神经保护
烟酰胺
NAD+激酶
烟酰胺腺嘌呤二核苷酸
视网膜神经节细胞
轴突
生物
喹啉酸
氧化应激
兴奋毒性
视网膜
药理学
神经科学
生物化学
程序性细胞死亡
细胞凋亡
色氨酸
氨基酸
酶
作者
James R. Tribble,Amin Otmani,Shanshan Sun,Sevannah A. Ellis,Gloria Cimaglia,Rupali Vohra,Melissa Jöe,Emma Lardner,Abinaya Priya Venkataraman,Alberto Domínguez‐Vicent,Eirini Kokkali,Seungsoo Rho,Gauti Jóhannesson,Robert W. Burgess,Peter G. Fuerst,Rune Brautaset,Miriam Kolko,James E. Morgan,Jonathan G Crowston,Marcela Votruba,Pete A. Williams
出处
期刊:Redox biology
[Elsevier]
日期:2021-07-01
卷期号:43: 101988-101988
被引量:83
标识
DOI:10.1016/j.redox.2021.101988
摘要
Nicotinamide adenine dinucleotide (NAD) is a REDOX cofactor and metabolite essential for neuronal survival. Glaucoma is a common neurodegenerative disease in which neuronal levels of NAD decline. We assess the effects of nicotinamide (a precursor to NAD) on retinal ganglion cells (the affected neuron in glaucoma) in normal physiological conditions and across a range of glaucoma relevant insults including mitochondrial stress and axon degenerative insults. We demonstrate retinal ganglion cell somal, axonal, and dendritic neuroprotection by nicotinamide in rodent models which represent isolated ocular hypertensive, axon degenerative, and mitochondrial degenerative insults. We performed metabolomics enriched for small molecular weight metabolites for the retina, optic nerve, and superior colliculus which demonstrates that ocular hypertension induces widespread metabolic disruption, including consistent changes to α-ketoglutaric acid, creatine/creatinine, homocysteine, and glycerophosphocholine. This metabolic disruption is prevented by nicotinamide. Nicotinamide provides further neuroprotective effects by increasing oxidative phosphorylation, buffering and preventing metabolic stress, and increasing mitochondrial size and motility whilst simultaneously dampening action potential firing frequency. These data support continued determination of the utility of long-term nicotinamide treatment as a neuroprotective therapy for human glaucoma.
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