Ophthalmic manifestations of NAA10-related and NAA15-related neurodevelopmental syndromes: Analysis of cortical visual impairment and refractive errors.

NAA10-related (Ogden syndrome) and NAA15-related neurodevelopmental syndrome are known to present with varying degrees of intellectual disability, hypotonia, congenital cardiac abnormalities, seizures, and delayed speech and motor development. However, the ophthalmic manifestations of NAA10 and NAA15 variants are not yet fully characterized or understood. This study analyzed the prevalence of six ophthalmic conditions (cortical visual impairment, myopia, hyperopia, strabismus, nystagmus, and astigmatism) in 67 patients with pathogenic (P) or likely pathogenic (LP) variants in the NAA10 cohort (54 inherited, 10 de novo; 65 missense, 2 frameshift) and 19 patients with (L)P variants in the NAA15 cohort (18 de novo; 8 frameshift, 4 missense, 4 nonsense, and 1 splice site). Patients were interviewed virtually or in-person to collect a comprehensive medical history verified by medical records. These records were then analyzed to calculate the prevalence of these ophthalmic manifestations in each cohort. Analysis revealed a higher prevalence of ophthalmic conditions in our NAA10 cohort compared to existing literature (myopia 25.4% vs. 4.7%; astigmatism 37.3% vs. 13.2%; strabismus 28.4% vs. 3.8%; CVI 22.4% vs. 8.5%, respectively). No statistically significant differences were identified in the prevalence of these conditions between the NAA10 and NAA15 variants. Our study includes novel neuroimaging of 13 NAA10 and 5 NAA15 probands, which provides no clear correlation between globe size and severity of comorbid ophthalmic disease. Finally, anecdotal evidence was compiled to underscore the importance of early ophthalmologic evaluations and therapeutic interventions.

A four-year-old girl with pathogenic variant in the NAA10 gene and precocious puberty - case report and literature review.

The NAA10 gene encodes N-alpha-acetyltransferase 10 which plays an important role in cell growth, differentiation, DNA damage, metastasis, apoptosis, stress response and autophagy. Defects in the NAA10 gene correlate with the diagnosis of NAA10-related syndrome (Ogden syndrome). The most common symptoms of NAA10-related syndrome are: global developmental delay, non-verbal or limited speech, autism spectrum disorder, feeding difficulties, motor delay, muscle tone disturbances, and long QT syndrome. To-date, there are about 100 patients who have been reported with this condition. The case report presents the clinical study of a girl aged 4 years and 3 months diagnosed with Ogden syndrome. She had many characteristic features of the disorder, as well as precocious puberty. This girl represents the case of a patient with p.Arg83Cys mutation in NAA10 gene as well as precocious puberty.

Longitudinal adaptive behavioral outcomes in Ogden syndrome by seizure status and therapeutic intervention.

Ogden syndrome, also known as NAA10-related neurodevelopmental syndrome, is a rare genetic condition associated with pathogenic variants in the NAA10 N-terminal acetylation family of proteins. The condition was initially described in 2011 and is characterized by a range of neurologic symptoms, including intellectual disability and seizures, as well as developmental delays, psychiatric symptoms, congenital heart abnormalities, hypotonia, and others. Previously published articles have described the etiology and phenotype of Ogden syndrome, mostly with retrospective analyses; herein, we report prospective data concerning its progress over time. The current study involves a total of 58 distinct participants; of these, 43 caregivers were interviewed using the Vineland-3 and answered a survey regarding therapy and other questions, 10 of whom completed the Vineland-3 but did not answer the survey, and 5 participants who answered the survey but have not yet performed the Vineland-3 due to language constraints. The average age at the time of the most recent assessment was 12.4 years, with individuals ranging in age from 11 months to 40.2 years. Using Vineland-3 scores, we show decline in cognitive function over time in individuals with Ogden syndrome (n = 53). Sub-domain analysis found the decline to be present across all modalities. In addition, we describe the nature of seizures in this condition in greater detail, as well as investigate how already-available non-pharmaceutical therapies impact individuals with NAA10-related neurodevelopmental syndrome. Additional investigation between seizure and non-seizure groups showed no significant difference in adaptive behavior outcomes. A therapy investigation showed speech therapy to be the most commonly used therapy by individuals with NAA10-related neurodevelopmental syndrome, followed by occupational and physical therapy, with more severely affected individuals receiving more types of therapy than their less-severe counterparts. Early intervention analysis was only significantly effective for speech therapy, with analyses of all other therapies being non-significant. Our study portrays the decline in cognitive function over time of individuals within our cohort, independent of seizure status, and therapies being received, and highlights the urgent need for the development of effective treatments for Ogden syndrome.

LncRNA RGMB-AS1 inhibits HMOX1 ubiquitination and NAA10 activation to induce ferroptosis in non-small cell lung cancer.

Ferroptosis, an iron-dependent regulated cell death caused by excessive lipid peroxide accumulation, has emerged as a promising therapeutic target in various cancers, including non-small cell lung cancer (NSCLC). In this study, we identified the long non-coding RNA RGMB-AS1 as a key regulator of ferroptosis in NSCLC. Mechanistically, RGMB-AS1 interacted with heme oxygenase 1 (HMOX1) and prevented its ubiquitination by the E3 ligase TRC8, leading to increased HMOX1 stability and enhanced ferroptosis. Additionally, RGMB-AS1 bound to the 82-87 amino acid region of N-alpha-acetyltransferase 10 (NAA10), stimulating its acetyltransferase activity and promoting the conversion of acetyl-CoA to HMG-CoA, further contributing to ferroptosis. The RGMB-AS1-HMOX1 and RGMB-AS1-NAA10 axes synergistically inhibited NSCLC growth both in vitro and in vivo. Clinically, low RGMB-AS1 expression was associated with advanced tumor stage and poor overall survival in NSCLC patients. Furthermore, adeno-associated virus-mediated RGMB-AS1 overexpression significantly suppressed tumor growth in mouse xenograft models. Our findings uncover a novel lncRNA-mediated regulatory mechanism of ferroptosis and highlight the potential of RGMB-AS1 as a prognostic biomarker and therapeutic target in NSCLC.

NAA10 gene expression is associated with mesenchymal transition, dedifferentiation, and progression of clear cell renal cell carcinoma.

INTRODUCTION: We aimed to investigate the expression and prognostic role of NAA10 in clear cell renal cell carcinoma (ccRCC). MATERIAL AND METHODS: We performed a gene expression and survival analysis based on the human cancer genome atlas database of ccRCC patients (TCGA-KIRC). RESULTS: The patients in the TCGA-KIRC (n = 537) were divided into two subgroups: NAA10-low and NAA10-high expression groups. NAA10-high ccRCC exhibited higher T stages (p = 0.002), a higher frequency of distant metastasis (p = 0.018), more advanced AJCC stages (p < 0.001), a lower overall survival time (p = 0.036), and a lower survival rate (p < 0.001). NAA10-high ccRCC was associated with increased activity of non-specific oncogenic pathways, including oxidative phosphorylation (p < 0.001) and cell cycle progression [G2 to M phase transition (p = 0.045) and E2F targets (p < 0.001)]. Additionally, the NAA10-high tumors showed reduced apoptosis via TRIAL pathways (p < 0.001) and increased levels of activity that promoted epithelial-mesenchymal transition (p = 0.026) or undifferentiation (p = 0.01). In ccRCC, NAA10 expression was found to be a negative prognostic factor in both non-metastatic (p < 0.001) and metastatic tumors (p = 0.032). CONCLUSIONS: In ccRCC, NAA10 expression was shown to be a negative prognostic factor related to tumor progression rather than tumor initiation, and high NAA10 expression promoted epithelial-mesenchymal transition and undifferentiation.

Multiple impacts of Naa10p on cancer progression: Molecular functions and clinical prospects.

Nα-acetyltransferase 10 protein (Naa10p) is known as the catalytic subunit of N-terminal acetyltransferases A (NatA) complex, associating with Naa15p to acetylate N-termini of the human proteome. Recent investigations have unveiled additional functions for Naa10p, encompassing lysine ε-acetylation and acetyltransferase-independent activities. Its pleiotropic roles have been implicated in diverse physiological and pathological contexts. Emerging evidence has implicated Naa10p in cancer progression, demonstrating dual attributes as an oncogene or a tumor suppressor contingent on the cancer type and acetyltransferase activity context. In this comprehensive review, we present a pan-cancer analysis aimed at elucidating the intricacies underlying Naa10p dysregulation in cancer. Our findings propose the potential involvement of c-Myc as a modulatory factor influencing Naa10p expression. Moreover, we provide a consolidated summary of recent advancements in understanding the intricate molecular underpinnings through which Naa10p contributes to cancer cell proliferation and metastasis. Furthermore, we delve into the multifaceted nature of Naa10p's roles in regulating cancer behaviors, potentially attributed to its interactions with a repertoire of partner proteins. Through an exhaustive exploration of Naa10p's functions, spanning its acetylation activity and acetyltransferase-independent functionalities, this review offers novel insights with implications for targeted therapeutic strategies involving this pivotal protein in the realm of cancer therapeutics.

Clinical manifestations in a Chinese girl with heterozygous de novo NAA10 variant c. 247C > T, p. (Arg83Cys): a case report.

The NAA10 gene encodes the catalytic subunit of the N-terminal acetyltransferase protein complex A (NatA), which is supposed to acetylate approximately 40% of the human proteins. After the advent of next-generation sequencing, more variants in the NAA10 gene and Ogden syndrome (OMIM# 300855) have been reported. Individuals with NAA10-related syndrome have a wide spectrum of clinical manifestations and the genotype-phenotype correlation is still far from being confirmed. Here, we report a three years old Chinese girl carrying a heterozygous de novo NAA10 [NM_003491: c. 247C > T, p. (Arg83Cys)] variant (dbSNP# rs387906701) (ClinVar# 208664) (OMIM# 300013.0010). The proband not only has some mild and common clinical manifestations, including dysmorphic features, developmental delay, obstructive hypertrophic cardiomyopathy, and arrhythmia, but also shows some rare clinical features such as exophthalmos, blue sclera, cutaneous capillary malformations, and adenoid hypertrophy. Our attempt is to expand the clinical phenotype associated with NAA10-related syndrome and explore genotype-phenotype correlation with such syndrome.

NAA10 overexpression dictates distinct epigenetic, genetic, and clinicopathological characteristics in adult gliomas.

NAA10 is a novel biomarker of cancer progression. The oncogenic and biological mechanisms of NAA10 in human malignancies are controversial and remain to be elucidated. Herein, we investigated the biological and clinicopathological implications of NAA10 gene expression in adult gliomas. We collected data from The Human Cancer Genome Atlas (TCGA) database, including patients from TCGA-GBM and TCGA-LGG projects. In total, there were 666 patients from the 2 projects (513 and 153 from TCGA-LGG and TCGA-GBM, respectively). Different analyses (pathway, DNA methylation, and survival analyses) require further specific case eliminations. Based on NAA10 expression, we divided 666 tumors into 2 subgroups: NAA10-high and NAA10-low glioma. There were higher activities of cell proliferation, metabolic reprogramming, DNA repair, angiogenesis, epithelial-mesenchymal transition, TNF-α, IL6/JAK/STAT6, mTORC1 signaling, and MYC targets in NAA10-high glioma, while P53, TGF-ß, Wnt, and Hedgehog pathways were highly expressed by NAA10-low gliomas. t-distributed stochastic neighbors embedding dimension reduction of DNA methylation also showed a high distribution of NAA10-high gliomas in distinct clusters. Survival analyses showed that high NAA10 expression was an independent prognostic factor. NAA10 expression dictated epigenetic, genetic, and clinicopathological differences in adult glioma. Further studies are required to investigate the detailed NAA10 oncogenic mechanisms and to validate NAA10 immunohistochemistry.

Phenotypic variability and gastrointestinal manifestations/interventions for growth in NAA10-related neurodevelopmental syndrome.

Our study of 61 children with NAA10-related neurodevelopmental syndrome, an X-linked disorder due to NAA10 gene variants, demonstrated a high prevalence of growth failure, with weight and height percentiles often in the failure-to-thrive diagnostic range; however, dramatic weight fluctuations and phenotypic variability is evidenced in the growth parameters of this population. Although never previously explored in depth, the gastrointestinal pathology associated with NAA10-related neurodevelopmental syndrome includes feeding difficulties in infancy, dysphagia, GERD/silent reflux, vomiting, constipation, diarrhea, bowel incontinence, and presence of eosinophils on esophageal endoscopy, in order from most to least prevalent. Additionally, the gastrointestinal symptom profile for children with this syndrome has been expanded to include eosinophilic esophagitis, cyclic vomiting syndrome, Mallory Weiss tears, abdominal migraine, esophageal dilation, and subglottic stenosis. Although the exact cause of poor growth in NAA10-related neurodevelopmental syndrome probands is unclear and the degree of contribution to this problem by GI symptomatology remains uncertain, an analysis including nine G-tube or GJ-tube fed probands demonstrates that G/GJ-tubes are overall efficacious with respect to improvements in weight gain and caregiving. The choice to insert a gastrostomy or gastrojejunal tube to aid with weight gain is often a challenging decision to make for parents, who may alternatively choose to rely on oral feeding, caloric supplementation, calorie tracking, and feeding therapy. In this case, if NAA10-related neurodevelopmental syndrome children are not tracking above the failure to thrive (FTT) range past 1 year of age despite such efforts, the treating physicians should be consulted regarding possibly undergoing G-tube placement to avoid prolonged growth failure. If G-tubes are not immediately inducing weight gain after insertion, recommendations could include altering formula, increasing caloric input, or exchanging a G-tube for a GJ-tube by means of a minimally invasive procedure.

Case report: Rare among ultrarare-Clinical odyssey of a new patient with Ogden syndrome.

Introduction: The definition of ultra-rare disease in terms of its prevalence varies between the sources, usually amounting to ca. 1 in 1.000.000 births. Nonetheless, there are even less frequent disorders, such as Ogden syndrome, which up to this day was diagnosed in less than 10 patients worldwide. They present typically with a variety of developmental defects, including postnatal growth retardation, psychomotor delay and hypotonia. This disorder is caused by the heterozygous mutations in NAA10 gene, which encodes N-alpha-acetyltransferase 10, involved in protein biosynthesis. Therefore, Ogden syndrome belongs to the broader group of genetic disorders, collectively described as NAA10-related syndrome. Case report: We present a case of a Polish male infant, born in 39. GW with c-section due to the pathological cardiotocography signal. Hypotrophy (2400 g) and facial dysmorphism were noted in the physical examination. From the first minute, the child required mechanical ventilation - a nasal continuous positive airway pressure. For the first 27 days, the patient was treated in a neonatal intensive care unit, where a series of examinations were conducted. On their basis, the presence of the following defects was determined: muscular ventricular septal defects, patent foramen ovale, pectus excavatum, clubfoot and axial hypotonia. Child was then consequently referred to the genetic clinic for counselling. Results of the tests allowed the diagnosis of Ogden syndrome. In the following months the patient's condition worsened due to the numerous pulmonary infections. Despite the advanced treatment including the variety of medications, the patient eventually died at the age of 10 months. Conclusion: This case report presents a tenth patient diagnosed with Ogden syndrome reported worldwide. It expands the morphologic and clinical phenotype, emphasizing the possible severity of pneumonological disorders in these patients, which may pose a greater threat to a child's life than more frequently described cardiovascular dysfunctions associated with this syndrome.

N-α-Acetyltransferase 10 inhibits invasion and metastasis of oral squamous cell carcinoma via regulating Pirh2-p53 signalling pathway.

N-α-Acetyltransferase 10 (NAA10) was reported to be involved in tumour invasion and metastasis in several of tumours. However, the role and mechanism of NAA10-mediated invasion and metastasis in oral squamous cell carcinoma (OSCC) remains undetermined. Herein, our study showed that NAA10 inhibits cell migration and invasion in vitro and attenuates the xenograft tumorigenesis in nude mice. Mechanistically, we demonstrated that there is a physical interaction between NAA10 and RelA/p65 in OSCC cells, thereby preventing RelA/p65-mediated transcriptional activation of Pirh2. Consequently, inhibition of Pirh2 increased p53 level and suppressed the expression of p53 downstream targets, matrix metalloprotein-2 (MMP-2) and MMP-9. Therefore, NAA10 may function as a tumour metastasis suppressor in the progression of OSCC by targeting Pirh2-p53 axis and might be a prognostic marker as well as a therapeutic target for OSCC.

iTRAQ and two-dimensional-LC-MS/MS reveal NAA10 is a potential biomarker in esophageal squamous cell carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is one of the most common and serious malignancies in China. However, the exact mechanisms of tumor progression are still unclear. Thus, identifying biomarkers for early diagnosis, prognostic and recurrence assessment of ESCC is necessary. EXPERIMENTAL DESIGN: iTRAQ was used to identify differentially expressed proteins (DEPs) in tumor tissues. N-alpha-acetyltransferase 10 (NAA10) is confirmed and validated by immunohistochemistry and western blotting. Furthermore, the effects of NAA10 on TE-1 cells were detected by CCK-8, colonies formation, anchorage-independent growth in soft agar, migration and transwell assays. LinkedOmics was used to identify differential gene expression with NAA10 and to analyze Gene Ontology and KEGG pathways. Coexpression gene network was conducted by the STRING database and Cytoscape software (MCODE plug-in). RESULTS: 516 DEPs were identified. NAA10 was downregulated in cancer tissues and selected for further confirmed. Furthermore, NAA10 can inhibit proliferation and tumorigenesis, and suppress migration and invasion of TE-1. Functional network analysis suggested that NAA10 regulates the ribosome pathways involving eight ribosomal proteins. CONCLUSION AND CLINICAL RELEVANCE: These findings clearly demonstrated that NAA10 is a tumor suppressor and novel potential biomarker for ESCC, laying a foundation for further study of the role of NAA10 in carcinogenesis.

Hydroxylation of the Acetyltransferase NAA10 Trp38 Is Not an Enzyme-Switch in Human Cells.

NAA10 is a major N-terminal acetyltransferase (NAT) that catalyzes the cotranslational N-terminal (Nt-) acetylation of 40% of the human proteome. Several reports of lysine acetyltransferase (KAT) activity by NAA10 exist, but others have not been able to find any NAA10-derived KAT activity, the latter of which is supported by structural studies. The KAT activity of NAA10 towards hypoxia-inducible factor 1α (HIF-1α) was recently found to depend on the hydroxylation at Trp38 of NAA10 by factor inhibiting HIF-1α (FIH). In contrast, we could not detect hydroxylation of Trp38 of NAA10 in several human cell lines and found no evidence that NAA10 interacts with or is regulated by FIH. Our data suggest that NAA10 Trp38 hydroxylation is not a switch in human cells and that it alters its catalytic activity from a NAT to a KAT.

Charting the N-Terminal Acetylome: A Comprehensive Map of Human NatA Substrates.

N-terminal acetylation (Nt-acetylation) catalyzed by conserved N-terminal acetyltransferases or NATs embodies a modification with one of the highest stoichiometries reported for eukaryotic protein modifications to date. Comprising the catalytic N-alpha acetyltransferase (NAA) subunit NAA10 plus the ribosome anchoring regulatory subunit NAA15, NatA represents the major acetyltransferase complex with up to 50% of all mammalian proteins representing potential substrates. Largely in consequence of the essential nature of NatA and its high enzymatic activity, its experimentally confirmed mammalian substrate repertoire remained poorly charted. In this study, human NatA knockdown conditions achieving near complete depletion of NAA10 and NAA15 expression resulted in lowered Nt-acetylation of over 25% out of all putative NatA targets identified, representing an up to 10-fold increase in the reported number of substrate N-termini affected upon human NatA perturbation. Besides pointing to less efficient NatA substrates being prime targets, several putative NatE substrates were shown to be affected upon human NatA knockdown. Intriguingly, next to a lowered expression of ribosomal proteins and proteins constituting the eukaryotic 48S preinitiation complex, steady-state levels of protein N-termini additionally point to NatA Nt-acetylation deficiency directly impacting protein stability of knockdown affected targets.

Naa12 compensates for Naa10 in mice in the amino-terminal acetylation pathway.

Amino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) is the major acetyltransferase, with 40-50% of all mammalian proteins being potential substrates. However, the overall role of amino-terminal acetylation on a whole-organism level is poorly understood, particularly in mammals. Male mice lacking Naa10 show no globally apparent in vivo amino-terminal acetylation impairment and do not exhibit complete embryonic lethality. Rather Naa10 nulls display increased neonatal lethality, and the majority of surviving undersized mutants exhibit a combination of hydrocephaly, cardiac defects, homeotic anterior transformation, piebaldism, and urogenital anomalies. Naa12 is a previously unannotated Naa10-like paralog with NAT activity that genetically compensates for Naa10. Mice deficient for Naa12 have no apparent phenotype, whereas mice deficient for Naa10 and Naa12 display embryonic lethality. The discovery of Naa12 adds to the currently known machinery involved in amino-terminal acetylation in mice.

Clinical Manifestations in a Girl with NAA10-Related Syndrome and Genotype-Phenotype Correlation in Females.

Since 2011, eight males with an X-linked recessive disorder (Ogden syndrome, MIM #300855) associated with the same missense variant p.(Ser37Pro) in the NAA10 gene have been described. After the advent of whole exome sequencing, many NAA10 variants have been reported as causative of syndromic or non-syndromic intellectual disability in both males and females. The NAA10 gene lies in the Xq28 region and encodes the catalytic subunit of the major N-terminal acetyltransferase complex NatA, which acetylates almost half the human proteome. Here, we present a young female carrying a de novo NAA10 [NM_003491:c.247C > T, p.(Arg83Cys)] variant. The 18-year-old girl has severely delayed motor and language development, autistic traits, postnatal growth failure, facial dysmorphisms, interventricular septal defect, neuroimaging anomalies and epilepsy. Our attempt is to expand and compare genotype-phenotype correlation in females with NAA10-related syndrome. A detailed clinical description could have relevant consequences for the clinical management of known and newly identified individuals.

Confirmation of Ogden syndrome as an X-linked recessive fatal disorder due to a recurrent NAA10 variant and review of the literature.

Ogden syndrome is a rare lethal X-linked recessive disorder caused by a recurrent missense variant (Ser37Pro) in the NAA10 gene, encoding the catalytic subunit of the N-terminal acetyltransferase A complex (NatA). So far eight boys of two different families have been described in the literature, all presenting the distinctive and recognizable phenotype, which includes mostly postnatal growth retardation, global severe developmental delay, characteristic craniofacial features, and structural cardiac anomalies and/or arrhythmias. Here, we report the ninth case of Ogden syndrome with an independent recurrence of the Ser37Pro variant. We were able to follow the clinical course of the affected boy and delineate the evolving phenotype from his birth until his unfortunate death at 7 months. We could confirm the associated phenotype as well as the natural history of this severe disease. By describing new presenting features, we are further expanding the clinical spectrum associated with Ogden syndrome and review other phenotypes associated with NAA10 variants.

Naa10p and IKKα interaction regulates EMT in oral squamous cell carcinoma via TGF-ß1/Smad pathway.

Epithelial-mesenchymal transition (EMT) has been contributed to increase migration and invasion of cancer cells. However, the correlate of Naa10p and IKKα with EMT in oral squamous cell carcinoma (OSCC) is not yet fully understood. In our present study, we found N-α-acetyltransferase 10 protein (Naa10p) and IκB kinase α (IKKα) were abnormally abundant in oral squamous cell carcinoma (OSCC). Bioinformatic results indicate that the expression of Naa10p and IKKα is correlated with TGF-ß1/Smad and EMT-related molecules. The Transwell migration, invasion, qRT-PCR and Western blot assay indicated that Naa10p repressed OSCC cell migration, invasion and EMT, whereas IKKα promoted TGF-ß1-mediated OSCC cell migration, invasion and EMT. Mechanistically, Naa10p inhibited IKKα activation of Smad3 through the interaction with IKKα directly in OSCC cells after TGF-ß1 stimulation. Notably, knockdown of Naa10p reversed the IKKα-induced change in the migration, invasion and EMT-related molecules in OSCC cells after TGF-ß1 stimulation. These findings suggest that Naa10p interacted with IKKα mediates EMT in OSCC cells through TGF-ß1/Smad, a novel pathway for preventing OSCC.

Down-regulation of NAA10 mediates the neuroprotection induced by sevoflurane preconditioning via regulating ERK1/2 phosphorylation.

OBJECTIVE: In the present study, the regulation mechanism of NAA10 (N-Alpha-Acetyltransferase 10) in sevoflurane preconditioning induced neuroprotective effect was explored. METHODS: Firstly, si-NAA10 or negative control (NC) were constructed for cell transfection and injected into intracerebroventricular of rats. Oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro and middle cerebral artery occlusion (MCAO) model in vivo were established to simulate cerebral I/R injury. QRT-PCR analysis and western blotting assay were performed to assess the expression of NAA10. TTC staining, neurological evaluation and cell counting kit-8 (CCK-8) were performed to evaluate the effect of NAA10 on sevoflurane induced neuroprotection. TUNEL assay and flow cytometry were used to detect the apoptosis in vivo and in vitro. RESULTS: It showed that sevoflurane preconditioning increased the expression of NAA10 in MCAO rats. TTC staining, TUNEL assay and neurological evaluation results suggested that si-NAA10 attenuated the neuroprotective effect of sevoflurane preconditioning against MCAO. CCK-8 assay, flow cytometry, qRT-PCR and western blot results showed that NAA10 mediated sevoflurane preconditioning-induced neuroprotection in vitro. Furthermore, western blot results showed that down-regulation of NAA10 could reverse the attenuation of ERK1/2 phosphorylation induced by sevoflurane preconditioning in vivo or in vitro. CONCLUSION: Down-regulation of NAA10 regulated ERK1/2 phosphorylation mediating sevoflurane preconditioning induced neuroprotective effects. The results revealed the regulatory mechanism of NAA10 in the neuroprotective effect of sevoflurane preconditioning.