Nan Zhang
Peking University
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Nan Zhang.
Neuroscience Letters | 2011
Jing Wang; Yun Zhang; Lu Tang; Nan Zhang; Dongsheng Fan
Resveratrol has recently been widely reported to be an age-delaying and neuroprotective compound, and it appears to produce these benefits by activating silent mating type information regulation 2 homolog 1 (SIRT1). However, the role that SIRT1 activation plays in the pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. In the present study, SIRT1 expression was found to be much lower in the mutant hSOD1G93A-bearing VSC4.1 cells compared to hSOD1wt cells when both were cultured in low-serum medium, indicating the involvement of SIRT1 activation defects in the pathogenesis of ALS under energetic stress. Further investigation revealed that a 24-h treatment with 0.5-20μM resveratrol had a dose-dependent protective effect on this ALS cell model, and the effects of resveratrol on increasing cell viability, preventing cell apoptosis and elevating cellular ATP levels through promoting mitochondria biogenesis were blocked by SIRT1 inhibition. This further demonstrated a role for SIRT1 activation in the protection of neuronal cells from degeneration. These findings suggest that resveratrol can protect the ALS cell model from mutant SOD1-mediated toxicity through up-regulating the expression of SIRT1, which represents a potential therapeutic target for preventing the motor neuron degeneration in ALS patients.
Neurobiology of Aging | 2013
Xiaolu Liu; Ming Lu; Lu Tang; Nan Zhang; Dehua Chui; Dongsheng Fan
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with unclear etiology. Recently, intermediate CAG repeat expansions in ATXN2, the gene responsible for spinocerebellar ataxia type 2 (SCA2), have been identified as a possible genetic risk factor for ALS. In this study, we analyzed the ATXN2 CAG repeat length in Chinese patients with ALS to evaluate the relationship between the genotype and phenotype. We studied 1,067 patients with ALS and 506 controls from mainland China (excluding Tibet). We collected clinical data and analyzed fluorescent PCR products to assess ATXN2 CAG repeat length in all of the samples. We observed that intermediate CAG repeat expansions in ATXN2 (CAG repeat length >30) were associated with ALS (p = 0.004). There was no significant difference in clinical characteristics between the groups with and without intermediate CAG repeat expansions in ATXN2. Our data indicate that, for ALS patients from mainland China, intermediate CAG repeat expansions in ATXN2 increase the risk of ALS but have no effect on disease phenotype.
Amyotrophic Lateral Sclerosis | 2015
Chengyu Li; Ying Ji; Lu Tang; Nan Zhang; Ji He; Shan Ye; Xiaolu Liu; Dongsheng Fan
Abstract The purpose of this study was to assess the frequency of optineurin (OPTN) mutation in amyotrophic lateral sclerosis (ALS) patients from mainland China, as well as to characterize the relationship between OPTN mutation and clinical phenotypes. We examined the coding region of OPTN in 511 unrelated Chinese sporadic ALS (SALS) subjects and 204 healthy controls using a PCR direct sequencing strategy. Nine OPTN variants were identified, of which four were novel missense mutations: c.407C > T (p.A136V), c.1184A > G (p.K395R), c.1352T > C (p.I451T), and c.1546G > C (p.E516Q) (all heterozygous). The remaining five variants were already present in single nucleotide polymorphism databases. Patients with OPTN mutations were characterized by spinal onset, although they showed differences in disease progression. In conclusion, this study provides a genetic epidemiological characterization of OPTN mutations in Chinese patients, and our results are consistent with the proposition that such mutations are common in Asian populations.
Amyotrophic Lateral Sclerosis | 2015
Yi Yang; Lu Tang; Nan Zhang; Lei Pan; Shinji Hadano; Dongsheng Fan
The purpose of this study was to identify SQSTM1 gene mutations, estimate survival based on the progression rate of the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) score (ΔFS), and characterize the relationships between SQSTM1 mutations and clinical phenotypes in Chinese ALS patients. We sequenced the SQSTM1 gene in 35 familial ALS patients, 436 sporadic ALS patients, and 384 healthy controls. SQSTM1 gene mutations were screened with PCR and direct sequencing; the correlations between genotype and phenotype and the progressive ALSFRS-R ratio were analyzed. Results revealed six heterozygous missense mutations in 471 ALS patients: c.241 G> A (p.E81K), c.717 C> A (p.N239K), c.889 G> A (p.G297S), c.1116 G> C (p.E372D), c.1162 C> T (p.P388S) and c.1175 C> T (p.P392 L). The gender ratio was 1:1, and the limb was the site of disease onset in mutation-positive patients. Notably, the ΔFS analysis revealed that the risk of death or tracheostomy was significantly increased in SQSTM1 mutation carriers (p < 0.05). In conclusion, E81K, N239K, G297S, E372D, P388S and P392 L were detected in the PB1, TRAF6, PEST and UBA domains, which are important to p62 function and prone to ALS. The incidence of ALS caused by the SQSTM1 mutation has increased from 30 to 35 worldwide.
Frontiers in Aging Neuroscience | 2016
Lu Chen; Xiaolu Liu; Lu Tang; Nan Zhang; Dongsheng Fan
Objectives: To investigate the effectiveness of riluzole in a long-term follow-up of cohort with sporadic amyotrophic lateral sclerosis (ALS) in a real-world study. Methods: Patients with ALS between 2007 and 2013 were followed up every 3 months. Survival and tracheotomy were predefined as primary outcome measures. The cumulative defined daily dose (cDDD) of riluzole was estimated. The patients in the riluzole group were classified into 1 of 3 subgroups according to the cDDD quartiles. Survival was analyzed using Kaplan–Meier and Cox regression analysis. Results: Of the 1,540 ALS patients, 415 (26.9%) used riluzole, and the remainder did not. In the riluzole group, the age at onset was greater (p = 0.016), the diagnostic delay was shorter (p < 0.0005), the body mass index (BMI) was higher (p < 0.0005), and the scores for both the functional rating scale (FRS) and the revised FRS (FRS-R) were higher (both p < 0.0005) than those of the control group. The median cDDD of riluzole was 28 (2,800 mg). Although Kaplan–Meier analysis did not reveal a significant difference between the two groups (p = 0.780), it showed that the prognosis of the beyond quartile 3 subgroup [cDDD ≥ 168 (16,800 mg)] was significantly better than that of the other groups [adjusted HR 0.488 (0.320–0.746), p = 0.001]. Conclusion: In China, older ALS patients and patients who had a higher BMI, shorter diagnostic delay, and higher FRS or FRS-R scores were more likely to use riluzole. Long-term use of riluzole was associated with a better prognosis for ALS patients, whereas short-term use had little effect on survival.
Neurobiology of Aging | 2014
Bin Cai; Lu Tang; Nan Zhang; Dongsheng Fan
The single-nucleotide polymorphisms (SNPs) rs6700125 and rs6690993 in FGGY (FLJ10986) were recently reported to be a susceptibility factor for sporadic amyotrophic lateral sclerosis (SALS) in Caucasian populations in genome-wide association studies. However, no such association was observed in other independent genome-wide association studies or replication studies in a European cohort or 2 small sample sizes of Chinese patients. We performed a large case-control study in a cohort consisting of 963 SALS cases and 1039 control subjects to examine the association between the 2 reported SNPs in FGGY and amyotrophic lateral sclerosisin Chinese patients. Our results did not find the SNP rs6690993 in FGGY is associated with Chinese SALS and cannot confirm that this FGGY SNP modulates the risk for SALS in the Chinese population.
Neurobiology of Aging | 2016
Lianping Xu; Jiao Li; Lu Tang; Nan Zhang; Dongsheng Fan
Several recent studies have reported that the MATR3 gene is associated with the risk of amyotrophic lateral sclerosis (ALS). We sequenced the MATR3 gene in 509 unrelated Chinese sporadic ALS patients and 560 control subjects. We identified a novel missense mutation p.Ser610Phe in one patient. We also detected 3 missense variants (p.Ala313Gly, p.Arg147Lys, and p.Gln347Lys) in 3 of the 560 healthy controls. Our results suggest that MATR3 may not be a common genetic factor in Chinese ALS patients.
Neurobiology of Aging | 2017
Shen Shen; Ji He; Lu Tang; Nan Zhang; Dongsheng Fan
Many genes have been found to be pathogenic for amyotrophic lateral sclerosis (ALS). Among them, the coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) has been reported to play a controversial role in ALS. We examined the coding region of this gene in 424 unrelated Chinese sporadic ALS subjects, 73 familial ALS subjects, and 204 healthy controls using a polymerase chain reaction-direct sequencing strategy. Two types of variants were identified, and of these, one variant (g.877C>T, p.P23L) was identified to be damaging, and the other one was (g.648G>A) in intron. The mutation (g.877C>T, p.P23L) has been previously reported in a Chinese frontotemporal dementia patient. Our study is the first to report the clinical heterogeneity of specific mutations in CHCHD10 in ALS in an Asian population and to report the possible new mutation hotspot. Our findings support the major role of CHCHD10 in the frontotemporal dementia-amyotrophic lateral sclerosis disease spectrum and stress the importance of mitochondrial abnormalities in the pathogenesis of diseases in Asian cohorts.
Amyotrophic Lateral Sclerosis | 2016
Jiao Li; Ji He; Lu Tang; Lu Chen; Lianping Xu; Yan Ma; Nan Zhang; Dongsheng Fan
Abstract TUBA4A gene has recently been identified as a potential candidate amyotrophic lateral sclerosis(ALS)-associated gene using exome-wide rare variant burden analysis. The identification of novel TUBA4A variants in Italian ALS patients further support the role of TUBA4A in ALS. We sequenced the coding region of exon 4 in the TUBA4A gene in a cohort consisting of 80 familial ALS probands, 500 sporadic ALS patients and 500 healthy control individuals. No TUBA4A causative variants were identified in the ALS patients. In conclusion, our current results did not find an association between TUBA4A and ALS in Chinese patients, and further studies will be required.
Neurobiology of Aging | 2018
Xiangyi Liu; Chujun Wu; Ji He; Nan Zhang; Dongsheng Fan
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. A recent study has identified mutations in the ANXA11 gene (encoding the calcium-binding protein annexin A11) associated with ALS. Mutation screening of ANXA11 protein-coding exons was performed in a Chinese cohort of 434 patients with sporadic ALS and 50 index patients with familial ALS. Polymerase chain reaction and Sanger sequencing were used for mutation detection. We failed to discover an N-terminal mutation, which was common in the Caucasian cohort. We revealed two rare heterozygous missense variants, c.878C>T (p.A293V) and c.921C>G (p.I307M), which are absent from the population databases and non-neurological controls. They are both located in the conserved annexin domain. The carriers of the mutation exhibited the classical ALS phenotype without cognitive impairment. Our results suggested that further functional studies for these variants are required to support the pathogenicity.