烟酰胺单核苷酸腺苷转移酶：它是一种烟酰胺腺嘌呤二核苷酸合酶……它是一种伴侣蛋白……它是一种神经保护剂。
NMNAT: It's an NAD synthase… It's a chaperone… It's a neuroprotector.
作者信息
Brazill Jennifer M, Li Chong, Zhu Yi, Zhai R Grace
机构信息
Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
出版信息
Curr Opin Genet Dev. 2017 Jun;44:156-162. doi: 10.1016/j.gde.2017.03.014. Epub 2017 Apr 23.
Abstract
Nicotinamide mononucleotide adenylyl transferases (NMNATs) are a family of highly conserved proteins indispensable for cellular homeostasis. NMNATs are classically known for their enzymatic function of catalyzing NAD synthesis, but also have gained a reputation as essential neuronal maintenance factors. NMNAT deficiency has been associated with various human diseases with pronounced consequences on neural tissues, underscoring the importance of the neuronal maintenance and protective roles of these proteins. New mechanistic studies have challenged the role of NMNAT-catalyzed NAD production in delaying Wallerian degeneration and have specified new mechanisms of NMNAT's chaperone function critical for neuronal health. Progress in understanding the regulation of NMNAT has uncovered a neuronal stress response with great therapeutic promise for treating various neurodegenerative conditions.
摘要
烟酰胺单核苷酸腺苷酸转移酶（NMNATs）是一类对细胞内稳态不可或缺的高度保守蛋白质家族。NMNATs传统上以其催化NAD合成的酶促功能而闻名，但也被誉为重要的神经元维持因子。NMNAT缺乏与多种人类疾病相关，对神经组织产生显著影响，凸显了这些蛋白质在神经元维持和保护作用中的重要性。新的机制研究对NMNAT催化的NAD产生在延缓沃勒氏变性中的作用提出了挑战，并明确了NMNAT伴侣功能对神经元健康至关重要的新机制。在理解NMNAT调控方面的进展揭示了一种神经元应激反应，对治疗各种神经退行性疾病具有巨大的治疗前景。
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NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD depletion.烟酰胺单核苷酸腺苷转移酶1通过阻断含 sterile α 和 armadillo 基序的蛋白1介导的烟酰胺腺嘌呤二核苷酸消耗来抑制轴突退化。
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An Atypical SCF-like Ubiquitin Ligase Complex Promotes Wallerian Degeneration through Regulation of Axonal Nmnat2.一种非典型的类SCF泛素连接酶复合物通过调节轴突Nmnat2促进沃勒变性。
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Nmnat1 protects neuronal function without altering phospho-tau pathology in a mouse model of tauopathy.NMNAT1 通过不改变磷酸化 tau 病理学来保护神经功能在 tau 病小鼠模型中。
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Two for the Price of One: A Neuroprotective Chaperone Kit within NAD Synthase Protein NMNAT2.买一送一：烟酰胺腺嘌呤二核苷酸合酶蛋白NMNAT2中的神经保护伴侣蛋白组合
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NMNAT2:HSP90 Complex Mediates Proteostasis in Proteinopathies.NMNAT2:HSP90复合物在蛋白病中介导蛋白质稳态。
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