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Translational Neurodegeneration

Lu Tang, Yan Ma, Xiao-Lu Liu, Lu Chen, Dong-Sheng Fan
Background: SOD1 mutations are the most common cause of amyotrophic lateral sclerosis (ALS) in non-Caucasian patients. Detailed natural history profiles of SOD1 -mutant patients will be beneficial for the strategy and interpretation of future SOD 1-targeted clinical practice. Methods: Mutational distribution, age at onset (AAO), site of onset, diagnostic delay, disease progression (rate of ALSFRS-R decrease, ΔFS) and survival were analysed. Further comparisons between heredity of disease, gender, and mutations were performed...
2019: Translational Neurodegeneration
Mauro Adenzato, Rosa Manenti, Ivan Enrici, Elena Gobbi, Michela Brambilla, Antonella Alberici, Maria Sofia Cotelli, Alessandro Padovani, Barbara Borroni, Maria Cotelli
Background: Parkinson's Disease (PD) with mild cognitive impairment (MCI) (PD-MCI) represents one of the most dreaded complications for patients with PD and is associated with a higher risk of developing dementia. Although transcranial direct current stimulation (tDCS) has been demonstrated to improve motor and non-motor symptoms in PD, to date, no study has investigated the effects of tDCS on Theory of Mind (ToM), i.e., the ability to understand and predict other people's behaviours, in PD-MCI...
2019: Translational Neurodegeneration
Jingjing Zhang, Yufei Liu, Xinyao Liu, Song Li, Cheng Cheng, Sheng Chen, Weidong Le
Background: Neuron-microglia communication plays a crucial role in the motor neurons (MNs) death in amyotrophic lateral sclerosis (ALS). Neurons can express chemokine (C-X3-C motif) ligand 1 (CX3CL1), which mediates microglial activation via interacting with its sole receptor CX3CR1 in microglia. In the present study, we aimed to investigate the dynamic changes of CX3CL1/CX3CR1 axis during microglial activation and MNs loss in SOD1G93A mouse model of ALS. Methods: qPCR, western blot and immunofluorescent staining were used to examine the mRNA and protein levels and localization of CX3CL1/CX3CR1 in the anterior horn region of spinal cord in both SOD1G93A mice and their age-matched wild type (WT) littermates at 40, 60, 90 and 120 days of age...
2018: Translational Neurodegeneration
Hongmei Li, Chia-Chen Liu, Hui Zheng, Timothy Y Huang
Background: Alzheimer's disease (AD) is a fatal disease that threatens the quality of life of an aging population at a global scale. Various hypotheses on the etiology of AD have been developed over the years to guide efforts in search of therapeutic strategies. Main body: In this review, we focus on four AD hypotheses currently relevant to AD onset: the prevailing amyloid cascade hypothesis, the well-recognized tau hypothesis, the increasingly popular pathogen (viral infection) hypothesis, and the infection-related antimicrobial protection hypothesis...
2018: Translational Neurodegeneration
Dan Zheng, Wei Xia, Zhong Quan Yi, Pan Wen Zhao, Jian Guo Zhong, Hai Cun Shi, Hua Liang Li, Zhen Yu Dai, Ping Lei Pan
[This corrects the article DOI: 10.1186/s40035-018-0134-8.].
2018: Translational Neurodegeneration
Zhenxin Zhang, Jian Wang, Shengdi Chen, Chunfeng Liu, Baorong Zhang, Rong Peng, Shenggang Sun, Xiangru Sun, Gang Zhao, Qiumin Qu, Yansheng Li, Suiqiang Zhu, Xiaoping Pan, Ming Shao, Yanping Wang
Background: Rasagiline is a monoamine oxidase-B inhibitor used for Parkinson's disease (PD) treatment, but its effectiveness on Chinese patients is unclear. This study aimed to evaluate the efficacy and safety of rasagiline monotherapy in Chinese patients with early PD. Methods: A 26-weeks, randomized, double-blind, placebo-controlled study has been performed at 15 sites in China and enrolled outpatients (≥35 years old) with idiopathic PD without a history of using any dopaminergic drugs...
2018: Translational Neurodegeneration
Bin Jiao, Qiying Sun, Zhenhua Yuan, Junling Wang, Lin Zhou, Xinxiang Yan, Beisha Tang, Lu Shen
Background: The TANK-Binding Kinase 1 ( TBK1 ) gene has recently been identified as the third or fourth most frequent cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the genetic contribution of TBK1 in a Chinese cohort. Methods: A total of 270 cases with ALS, FTD, or their combination were recruited into this study. All the coding exons of TBK1 and intron-exon boundaries were sequenced using Sanger sequencing...
2018: Translational Neurodegeneration
William R Swindell, Krzysztof Bojanowski, Mark S Kindy, Raymond M W Chau, Dorothy Ko
Background: Amyotrophic lateral sclerosis (ALS) is currently an incurable disease without highly effective pharmacological treatments. The peptide drug GM604 (GM6 or Alirinetide) was developed as a candidate ALS therapy, which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic profile. GM6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways, but mechanisms of action are not fully understood. Methods: This study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following GM6 treatment (6, 24 and 48 h)...
2018: Translational Neurodegeneration
Dan Zhen, Wei Xia, Zhong Quan Yi, Pan Wen Zhao, Jian Guo Zhong, Hai Cun Shi, Hua Liang Li, Zhen Yu Dai, Ping Lei Pan
Background: Resting-state functional magnetic resonance imaging studies using a regional homogeneity (ReHo) method have reported that amnestic mild cognitive impairment (aMCI) was associated with abnormalities in local functional connectivity. However, their results were not conclusive. Methods: Seed-based d Mapping was used to conduct a coordinate-based meta-analysis to identify consistent ReHo alterations in aMCI. Results: We identified 10 studies with 11 datasets suitable for inclusion, including 378 patients with aMCI and 435 healthy controls...
2018: Translational Neurodegeneration
Kangmu Ma, Xiaobei Deng, Xiaohuan Xia, Zhaohuan Fan, Xinrui Qi, Yongxiang Wang, Yuju Li, Yizhao Ma, Qiang Chen, Hui Peng, Jianqing Ding, Chunhong Li, Yunlong Huang, Changhai Tian, Jialin C Zheng
Background: Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation. Methods: Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2...
2018: Translational Neurodegeneration
Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D Allan Butterfield, Marzia Perluigi, Fabio Di Domenico
Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression...
2018: Translational Neurodegeneration
Kaicheng Li, Xiao Luo, Qingze Zeng, Yeerfan Jiaerken, Xiaojun Xu, Peiyu Huang, Zhujing Shen, Jingjing Xu, Chao Wang, Jiong Zhou, Min-Ming Zhang
Background: Individuals with subjective memory complaints (SMC) feature a higher risk of cognitive decline and clinical progression of Alzheimer's disease (AD). However, the pathological mechanism underlying SMC remains unclear. We aimed to assess the intrinsic connectivity network and its relationship with AD-related pathologies in SMC individuals. Methods: We included 44 SMC individuals and 40 normal controls who underwent both resting-state functional MRI and positron emission tomography (PET)...
2018: Translational Neurodegeneration
Haichen Niu, Lingyu Shen, Tongzhou Li, Chao Ren, Sheng Ding, Lei Wang, Zhonghai Zhang, Xiaoyu Liu, Qiang Zhang, Deqin Geng, Xiujuan Wu, Haiying Li
Background: Parkinson's disease (PD) is a neurodegenerative disease characterized by intraneuronal Lewy Body (LB) aggregates composed of misfolded alpha-synuclein (α-syn). The spread of misfolded α-syn follows a typical pattern: starting in the olfactory bulb (OB) and the gut, this pathology is followed by the progressive invasion of misfolded α-syn to the posterior part of the brain. It is unknown whether the administration of human mutant alpha-synuclein (hm-α-syn, a human mutation which occurs in familial PD) into the OB of rats would trigger similar α-syn propagation and subsequently cause pathological changes in broader brain fields associated to PD and establish an animal model of prodromal PD...
2018: Translational Neurodegeneration
Xin Jiang, Tao Zhang, Haifang Wang, Tao Wang, Meiling Qin, Puhua Bao, Ruiqi Wang, Yuwei Liu, Hung-Chun Chang, Jun Yan, Jin Xu
Background: Circadian rhythms are oscillating physiological and behavioral changes governed by an internal molecular clock, and dysfunctions in circadian rhythms have been associated with ageing and various neurodegenerative diseases. However, the evidence directly connecting the neurodegeneration-associated proteins to circadian control at the molecular level remains sparse. Methods: Using meta-analysis, synchronized animals and cell lines, cells and tissues from FUS R521C knock-in rats, we examined the role of FUS in circadian gene expression regulation...
2018: Translational Neurodegeneration
Maowen Ba, Guoping Yu, Min Kong, Hui Liang, Ling Yu
Background: Rapid eye movement sleep behavior disorder (RBD) is associated with cognitive decline in early Parkinson's disease (PD). However, the underlyling basis for this association remains unclear. Methods: Parkinson's Progression Marker's Initiative (PPMI) subjects underwent baseline RBD testing with RBD sleep questionnaire (RBDSQ). Serial assessments included measures of motor symptoms, non-motor symptoms (NMS), neuropsychological assessment, blood and cerebrospinal fluid (CSF) biomarkers...
2018: Translational Neurodegeneration
Hua Zhang, Kok Pin Ng, Joseph Therriault, Min Su Kang, Tharick A Pascoal, Pedro Rosa-Neto, Serge Gauthier
Background: Visinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively. Phosphorylated tau (p-tau) reflects the neuropathology of Alzheimer's disease (AD) and is useful as diagnostic markers for AD. However, it is unknown whether these biomarkers have similar or complementary information in AD. Methods: We stratified 121 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN), stable mild cognitive impairment (sMCI), progressive MCI (pMCI), and dementia due to AD...
2018: Translational Neurodegeneration
Yuhuan Shi, Wanying Huang, Yu Wang, Rui Zhang, Lina Hou, Jianrong Xu, Zhuibai Qiu, Qiong Xie, Hongzhuan Chen, Yongfang Zhang, Hao Wang
Background: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder, which is the most common form of dementia. Intensive efforts have been made to find effective and safe treatment against AD. Acetylcholinesterase inhibitors (AChEIs) have been widely used for the treatment of mild to moderate AD. In this study, we investigated the effect of Bis(9)-(-)-Meptazinol (B9M), a novel potential dual-binding acetylcholinesterase (AChE) inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD...
2018: Translational Neurodegeneration
Chao Gao, Stephen Smith, Michael Lones, Stuart Jamieson, Jane Alty, Jeremy Cosgrove, Pingchen Zhang, Jin Liu, Yimeng Chen, Juanjuan Du, Shishuang Cui, Haiyan Zhou, Shengdi Chen
Background: There is an urgent need for developing objective, effective and convenient measurements to help clinicians accurately identify bradykinesia. The purpose of this study is to evaluate the accuracy of an objective approach assessing bradykinesia in finger tapping (FT) that uses evolutionary algorithms (EAs) and explore whether it can be used to identify early stage Parkinson's disease (PD). Methods: One hundred and seven PD, 41 essential tremor (ET) patients and 49 normal controls (NC) were recruited...
2018: Translational Neurodegeneration
Rodolfo G Gatto, Manish Y Amin, Daniel Deyoung, Matthew Hey, Thomas H Mareci, Richard L Magin
Background: Amyotrophic lateral sclerosis (ALS) is a disease characterized by a progressive degeneration of motor neurons leading to paralysis. Our previous MRI diffusion tensor imaging studies detected early white matter changes in the spinal cords of mice carrying the G93A-SOD1 mutation. Here, we extend those studies using ultra-high field MRI (17.6 T) and fluorescent microscopy to investigate the appearance of early structural and connectivity changes in the spinal cords of ALS mice...
2018: Translational Neurodegeneration
Ming-Shu Mo, Gui-Hua Li, Cong-Cong Sun, Shu-Xuan Huang, Lei Wei, Li-Min Zhang, Miao-Miao Zhou, Zhuo-Hua Wu, Wen-Yuan Guo, Xin-Ling Yang, Chao-Jun Chen, Shao-Gang Qu, Jian-Xing He, Ping-Yi Xu
Background: Abnormal expression of major histocompatibility complex class I (MHC-I) is increased in dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Low-molecular-mass protein 7 (β5i) is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells. Methods: In this study, we investigated the role of β5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and vivo ...
2018: Translational Neurodegeneration
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