Authors: Wang, Hongmei | Ma, Jianfang | Tan, Yuyan | Wang, Zhiquan | Sheng, Chengyu | Chen, Shengdi | Ding, Jianqing
Article Type: Research Article
Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder initiated by the aggregation of amyloid-β peptide (Aβ). Macroautophagy, which is essential for cell survival as well as the promotion of cell death, has been observed extensively in AD brains or transgenic mice overexpressing Aβ protein precursor. However, the role of macroautophagy in the pathogenesis of AD is unclear. In this study, we showed that Aβ1-42 triggered autophagic cell death in both human glioma cell line (U87 cell) and human neuroblastoma cell line (SH-SY5Y cell). Aβ1-42 -induced cytotoxicity and autophagic cell death were blocked by the autophagy inhibitor 3-methyladenine (3-MA) or by small …interfering RNA against the autophagy gene Beclin-1. Reactive oxygen species (ROS) accumulation was also detected in both Aβ1-42 treated cell lines and this accumulation was not affected by 3-MA. Moreover, pretreatment with the ROS scavenger N-acetylcysteine inhibited ROS accumulation and autophagic cell death induced by Aβ1-42 , suggesting that Aβ1-42 -induced ROS accumulation might trigger the onset of autophagy and subsequent autophagic cell death. These findings provide further insights into the mechanisms underlying Aβ-induced cytotoxicity. Show more
Keywords: Apoptosis, autophagic cell death, Beclin-1, N-acetylcysteine, reactive oxygen species
DOI: 10.3233/JAD-2010-091207
Citation: Journal of Alzheimer's Disease, vol. 21, no. 2, pp. 597-610, 2010
Authors: Deng, Yulei | Wei, Jing | Cheng, Jia | Zhong, Ping | Xiong, Zhe | Liu, Aiyi | Lin, Lin | Chen, Shengdi | Yan, Zhen
Article Type: Research Article
Abstract: The loss of synaptic structure and function has been linked to the cognitive impairment of Alzheimer’s disease (AD). Dysregulation of the actin cytoskeleton, which plays a key role in regulating the integrity of synapses and the transport of synaptic proteins, has been suggested to contribute to the pathology of AD. In this study, we found that glutamate receptor surface expression and synaptic function in frontal cortical neurons were significant diminished in a familial AD (FAD) model, which was correlated with the reduction of phosphorylated cofilin, a key protein regulating the dynamics of actin filaments. Injecting a cofilin dephosphorylation inhibitory peptide …to FAD mice led to the partial rescue of the surface expression of AMPA and NMDA receptor subunits, as well as the partial restoration of AMPAR- and NMDAR-mediated synaptic currents. Moreover, the impaired working memory and novel object recognition memory in FAD mice were partially ameliorated by injections of the cofilin dephosphorylation inhibitory peptide. These results suggest that targeting the cofilin-actin signaling holds promise to mitigate the physiological and behavioral abnormality in AD. Show more
Keywords: Actin, Alzheimer’s disease, cofilin, glutamate receptors, novel object recognition memory, prefrontal cortex, working memory
DOI: 10.3233/JAD-160167
Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1419-1432, 2016
Authors: Wang, Ying | Wang, Ying | Sui, Yi | Yu, Hongshuang | Shen, Xiaoheng | Chen, Shengdi | Pei, Gang | Zhao, Jian | Ding, Jianqing
Article Type: Research Article
Abstract: Alzheimer's disease (AD) is a common neurodegenerative disease affecting cognitive function in the elderly, which is characterized by the presence of extracellular deposits of insoluble amyloid-β plaques and neuronal loss. Modern pharmacology and drug development usually follow a single-target principle, which might contribute to the failure of most compounds in clinical trials against AD. Considering AD is a multifactorial disease, a combination therapeutic strategy that applies drugs with different mechanisms would be an alternative way. Smart Soup (SS), a Traditional Chinese Medicine formula, is composed of three herbaceous plants and has been applied in the treatment of amnesia in China …for hundreds of years. In this work, we studied the clinical potency of the combination of SS and Aricept in AD therapy. In the in vivo model, both longevity and locomotive activity of AD transgenic Drosophila were improved remarkably in the combined medicine treated group. We also observed less amyloid-β deposition and retarded neuronal loss following the combined drug treatment. In the retrospective cohort study, we found the combination therapy exerted better therapeutic effect on AD patients. Our study revealed that combination therapy with multiple drug targets did have a better therapeutic outcome. It provides a new strategy to develop an optimum pharmaceutical approach against AD. Show more
Keywords: Alzheimer's disease, Traditional Chinese Medicine, Smart Soup (SS), Aricept, combination therapy
DOI: 10.3233/JAD-143183
Citation: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1185-1195, 2015
Authors: Wang, Hualong | Xu, Ying | Ren, Rujing | Yao, Feng | Chen, Mei | Sheng, Zhihua | Guo, Xin | Li, Yan | Chen, Shengdi | Wang, Gang
Article Type: Research Article
Abstract: Background: Previous studies revealed that abnormal blood pressure (BP) plays an important role in the pathogenesis of Alzheimer’s disease (AD). However, little is known about the ambulatory BP characteristics of AD in the mild or severe stage. Objective: We explored the ambulatory BP characteristics of AD in the mild or severe stage. Methods: In the present study, 106 AD patients (42.5%male, average age 81.6 years) were enrolled from three centers in China. Clinal BP measurements at the supine and standing positions, neurological evaluations, and the 24 h ambulatory BP monitoring were performed. Results: In the 106 AD patients, 49.2%, 36.8%, and …70%of patients had 24 h, daytime, and nighttime systolic hypertension, respectively, while 19.8%, 29.2%, and 5.7%had 24 h, daytime, and nighttime diastolic hypotension. The prevalence of the reduced and reverse dipping pattern was 34.0%and 48.1%for systolic BP and 32.1%and 45.3%for diastolic BP, respectively. The daytime diastolic BP was significantly correlated with cognitive performance. After adjustment for age, sex, and body mass index, only daytime diastolic BP was associated with remarkable cognitive deterioration (p ≤0.008). Further, AD patients in the severe stage had significantly lower levels of the 24 h, daytime, and nighttime diastolic BP, compared with those in the mild stage. Conclusion: In general, AD patients were featured with high nighttime systolic BP, low daytime diastolic BP, and abnormal circadian BP rhythm of reduced and reverse dipping. The diastolic BP, especially daytime diastolic BP, was adversely correlated with the cognitive deterioration in AD. Show more
Keywords: Alzheimer’s disease, ambulatory blood pressure, blood pressure variability, dipping
DOI: 10.3233/JAD-210679
Citation: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1333-1339, 2021
Authors: Du, Juanjuan | Huang, Pei | Qian, Yiwei | Yang, Xiaodong | Cui, Shishuang | Lin, Yiqi | Gao, Chao | Zhang, Pingchen | He, Yixi | Xiao, Qin | Chen, Shengdi
Article Type: Research Article
Abstract: Background and Objective: To explore the alterations of microbial 16s ribosomal (rRNA) gene in the feces and blood of Chinese patients with multiple system atrophy (MSA) and its relationships with clinical features. Methods: 40 MSA patients (MSA-P/MSA-C: 23/17) and their healthy spouses were recruited. Fecal and blood microbiota were investigated by high-throughput IllUmina Miseq sequencing targeted on the V3-V4 functional region of 16s rRNA gene. The relationships between microbiota and clinical characteristics were analyzed. Results: The abundances of Lactobacillus, Gordonibacter, Phascolarctobacterium, and Haemophilus in feces and abundances of Leucobacter, and Bacteroides in blood were different between MSA patients and healthy …controls (HC). Combining the taxa from feces and blood, six genera were identified to be predictive of MSA, achieving an area under the curve (AUC) of 0.853. The abundances of Phascolarctobacterium and Ruminococcus in feces were lower in MSA-P than those in MSA-C. The abundances of Blastococcus, Bacillus, and Acinetobacter in blood were different between MSA subtypes. These five genera differentiated MSA subtypes with an AUC of 0.898. Functional predictions indicated that gene functions involving biosynthetic metabolism and bacterial secretion systems were significantly different between the MSA and HC. The differential genera were associated with disease duration, anxiety, and autonomic dysfunctions. Conclusions: We confirmed the alterations of microbial 16s rRNA gene in the feces and blood occurs in Chinese patients with MSA. Microbiota dysbiosis was related to MSA clinical manifestations. Elucidating these differences in microbiomes will be helpful to improve our knowledge of the microbiota in the pathogenesis of MSA. Show more
Keywords: Multiple system atrophy, 16s rRNA gene, microbiota, blood, feces
DOI: 10.3233/JPD-191612
Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 711-721, 2019
Authors: Du, Juanjuan | Cui, Shishuang | Huang, Pei | Gao, Chao | Zhang, Pingchen | Liu, Jin | Li, Hongxia | Huang, Maoxin | Shen, Xin | Liu, Zixian | Chen, Zilu | Tan, Yuyan | Chen, Shengdi
Article Type: Research Article
Abstract: Background: Multiple system atrophy (MSA) is an intractable neurodegenerative disorder with poorly understanding of prognostic factors. Objective: The purpose of this retrospective longitudinal study was to explore the main predictors of survival of MSA patients with new clinical subtypes based on cluster analysis. Methods: A total of 153 Chinese MSA patients were recruited in our study. The basic demographic data and motor and nonmotor symptoms were assessed. Cluster and principal component analysis (PCA) were used to eliminate collinearity and search for new clinical subtypes. The multivariable Cox regression was used to find factors associated with survival in MSA patients. Results: …The median survival time from symptom onset to death (estimated using data from all patients by Kaplan-Meier analysis) was 6.3 (95% CI = 6.1–6.7) years. The survival model showed that a shorter survival time was associated with motor principal component (PC)1 (HR = 1.71, 95% CI: 1.26–2.30, p < 0.001) and nonmotor PC3 (HR = 1.68, 95% CI: 1.31–2.10, p < 0.001) through PCA. Four clusters were identified: Cluster 1 (mild), Cluster 2 (mood disorder-dominant), Cluster 3 (axial symptoms and cognitive impairment-dominant), and Cluster 4 (autonomic failure-dominant). Multivariate Cox regression indicated that Cluster 3 (HR = 4.15, 95% CI: 1.73–9.90, p = 0.001) and Cluster 4 (HR = 4.18, 95% CI: 1.73–10.1, p = 0.002) were independently associated with shorter survival time. Conclusion: More serious motor symptoms, axial symptoms such as falls and dysphagia, orthostatic hypotension, and cognitive impairment were associated with poor survival in MSA via PCA and cluster analysis. Show more
Keywords: Cluster analysis, multiple system atrophy, principal component analysis, prognosis
DOI: 10.3233/JPD-225127
Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 937-946, 2023
Authors: Su, Wen | Huang, Pei | Ma, Xinxin | Shang, Huifang | Ye, Qinyong | Cheng, Oumei | Chan, Piu | Liu, Chunfeng | Liu, Weiguo | Tang, Beisha | Wang, Lijuan | Zhang, Baorong | Wang, Tao | Shao, Ming | Xie, Anmu | Chen, Xianwen | Zhu, Xiaodong | Wang, Jian | Tao, Enxiang | Chen, Shengdi | Chen, Haibo
Article Type: Research Article
Abstract: Background: Nocturnal symptoms have a significant effect on the quality of life in Parkinson’s disease (PD) patients. Objective: This study aimed to investigate the prevalence and associated factors of nocturnal symptoms in Chinese PD patients. Methods: This multicenter cross-sectional study included 1,500 patients with primary PD from 18 centers in China was carried out between February 2019 and February 2020. Questionnaires including Parkinson’s disease sleep scale 2 (PDSS-2), Parkinson’s disease questionnaire 8 (PDQ-8), Beck depression inventory (BDI), and generalized anxiety disorder scale 7 (GAD-7) were used to assess nocturnal symptoms, quality of life, depression, and anxiety. Results: Among 1,500 Chinese …PD patients, 576 (38.4%) reported nocturnal symptoms. Of them, 59.2% were older than 65 years. The PDQ-8 total score was higher in patients with nocturnal symptoms (p < 0.01). Moderate and severe depression was reported more often in patients with nocturnal symptoms (p < 0.01), and the occurrence and severity of anxiety were higher as well (p < 0.01). Longer disease duration and higher Hoehn-Yahr (HY) stage were independently associated with nocturnal symptoms (p < 0.01). Education level, depression, disease course, HY stage, and nocturnal symptoms were related to the quality of life in Chinese PD patients (p < 0.01). Conclusion: Our study found that 38.4% of Chinese PD patients have nocturnal symptoms, even in early and mid-stage PD. Nocturnal symptoms were associated with worse quality of life and higher incidences of depression and anxiety. Nocturnal symptoms should be included in the assessment and care plan, especially in patients with longer disease courses and higher HY stages. Show more
Keywords: Parkinson’s disease, nocturnal symptoms, quality of life, PDSS-2, associated factors
DOI: 10.3233/JPD-230060
Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 1061-1071, 2023
