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Translational Neurodegeneration

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https://www.readbyqxmd.com/read/28439409/serial-deletion-reveals-structural-basis-and-stability-for-the-core-enzyme-activity-of-human-glutaminase-1-isoforms-relevance-to-excitotoxic-neurodegeneration
#1
Yuju Li, Justin Peer, Runze Zhao, Yinghua Xu, Beiqing Wu, Yi Wang, Changhai Tian, Yunlong Huang, Jialin Zheng
BACKGROUND: Glutaminase 1 is a phosphate-activated metabolic enzyme that catalyzes the first step of glutaminolysis, which converts glutamine into glutamate. Glutamate is the major neurotransmitter of excitatory synapses, executing important physiological functions in the central nervous system. There are two isoforms of glutaminase 1, KGA and GAC, both of which are generated through alternative splicing from the same gene. KGA and GAC both transcribe 1-14 exons in the N-terminal, but each has its unique C-terminal in the coding sequence...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28396731/clinical-features-and-genotype-phenotype-correlation-analysis-in-patients-with-atl1-mutations-a-literature-reanalysis
#2
Guo-Hua Zhao, Xiao-Min Liu
BACKGROUND: The hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders. Approximately 10% of the autosomal dominant (AD) HSPs (ADHSPs) have the spastic paraplegia 3A (SPG3A) genotype which is caused by ATL1 gene mutations. Currently there are more than 60 reported ATL1 gene mutations and the genotype-phenotype correlation remains unclear. The study aims to investigate the genotype-phenotype correlation in SPG3A patients. METHODS: We performed a reanalysis of the clinical features and genotype-phenotype correlations in 51 reported studies exhibiting an ATL1 gene mutation...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28360997/imaging-biomarkers-in-parkinson-s-disease-and-parkinsonian-syndromes-current-and-emerging-concepts
#3
REVIEW
Usman Saeed, Jordana Compagnone, Richard I Aviv, Antonio P Strafella, Sandra E Black, Anthony E Lang, Mario Masellis
Two centuries ago in 1817, James Parkinson provided the first medical description of Parkinson's disease, later refined by Jean-Martin Charcot in the mid-to-late 19th century to include the atypical parkinsonian variants (also termed, Parkinson-plus syndromes). Today, Parkinson's disease represents the second most common neurodegenerative disorder with an estimated global prevalence of over 10 million. Conversely, atypical parkinsonian syndromes encompass a group of relatively heterogeneous disorders that may share some clinical features with Parkinson's disease, but are uncommon distinct clinicopathological diseases...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28360996/the-role-of-cognitive-activity-in-cognition-protection-from-bedside-to-bench
#4
REVIEW
Bin-Yin Li, Ying Wang, Hui-Dong Tang, Sheng-Di Chen
BACKGROUND: Cognitive decline poses a great concern to elderly people and their families. In addition to pharmacological therapies, several varieties of nonpharmacological intervention have been developed. Most training trials proved that a well-organized task is clinically effective in cognition improvement. MAIN BODY: We will first review clinical trials of cognitive training for healthy elders, MCI and AD patients, respectively. Besides, potential neuroprotective and compensatory mechanisms in animal models of AD are discussed...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28293421/protein-misfolding-in-neurodegenerative-diseases-implications-and-strategies
#5
REVIEW
Patrick Sweeney, Hyunsun Park, Marc Baumann, John Dunlop, Judith Frydman, Ron Kopito, Alexander McCampbell, Gabrielle Leblanc, Anjli Venkateswaran, Antti Nurmi, Robert Hodgson
A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic collapse. Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease, including synthesis, chaperone-assisted folding and trafficking, and degradation via the proteasome and autophagy pathways. Other therapies, like mTOR inhibitors and activators of the heat shock response, can rebalance the entire proteostatic network...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28265351/elevated-axonal-membrane-permeability-and-its-correlation-with-motor-deficits-in-an-animal-model-of-multiple-sclerosis
#6
Gary Leung, Melissa Tully, Jonathan Tang, Shengxi Wu, Riyi Shi
BACKGROUND: It is increasingly clear that in addition to myelin disruption, axonal degeneration may also represent a key pathology in multiple sclerosis (MS). Hence, elucidating the mechanisms of axonal degeneration may not only enhance our understanding of the overall MS pathology, but also elucidate additional therapeutic targets. The objective of this study is assess the degree of axonal membrane disruption and its significance in motor deficits in EAE mice. METHODS: Experimental Autoimmune Encephalomyelitis was induced in mice by subcutaneous injection of myelin oligodendrocyte glycoprotein/complete Freud's adjuvant emulsion, followed by two intraperitoneal injections of pertussis toxin...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28239455/the-underlying-mechanism-of-prodromal-pd-insights-from-the-parasympathetic-nervous-system-and-the-olfactory-system
#7
REVIEW
Shu-Ying Liu, Piu Chan, A Jon Stoessl
Neurodegeneration of Parkinson's disease (PD) starts in an insidious manner, 30-50% of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis. Prodromal stage of the disease, during which the disease pathology has started but is insufficient to result in clinical manifestations, offers a valuable window for disease-modifying therapies. The most focused underlying mechanisms linking the pathological pattern and clinical characteristics of prodromal PD are the prion hypothesis of alpha-synuclein and the selective vulnerability of neurons...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28184302/the-role-of-exosomes-in-the-pathogenesis-of-alzheimer-disease
#8
REVIEW
Tingting Xiao, Weiwei Zhang, Bin Jiao, Chu-Zheng Pan, Xixi Liu, Lu Shen
Exosomes are small vesicles secreted by most cell types including neurons that function in intercellular communication through transfer of their cargo or encapsulate and eliminate unnecessary cellular components and therefore have a broad impact on nerve development, activation and regeneration. In addition, exosomes have been observed to be involved in spreading pathological misfolded proteins, thereby leading to the onset and propagation of disease. Alzheimer disease (AD) is the most common form of dementia and characterized by two types of lesions: amyloid plaques and neurofibrillary tangles...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28149509/music-therapy-is-a-potential-intervention-for-cognition-of-alzheimer-s-disease-a-mini-review
#9
REVIEW
Rong Fang, Shengxuan Ye, Jiangtao Huangfu, David P Calimag
Alzheimer's Disease (AD) is a global health issue given the increasing prevalence rate and the limitations of drug effects. As a consequent, non-pharmacological interventions are of importance. Music therapy (MT) is a non-pharmacological way with a long history of use and a fine usability for dementia patients. In this review, we will summarize different techniques, diverse clinical trials, and the mechanisms of MT as it is helpful to the cognition in AD, providing reference for future research. Many articles have demonstrated that MT can reduce cognitive decline especially in autobiographical and episodic memories, psychomotor speed, executive function domains, and global cognition...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28105331/opioid-system-in-l-dopa-induced-dyskinesia
#10
REVIEW
Jing Pan, Huaibin Cai
L-3, 4-Dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) is a major clinical complication in the treatment of Parkinson's disease (PD). This debilitating side effect likely reflects aberrant compensatory responses for a combination of dopaminergic neuron denervation and repeated L-DOPA administration. Abnormal endogenous opioid signal transduction pathways in basal ganglia have been well documented in LID. Opioid receptors have been targeted to alleviate the dyskinesia. However, the exact role of this altered opioid activity is remains under active investigation...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28035283/stroke-like-onset-of-brain-stem-degeneration-presents-with-unique-mri-sign-and-heterozygous-nmnat2-variant-a-case-report
#11
Alexander Schulz, Franziska Wagner, Martin Ungelenk, Ingo Kurth, Christoph Redecker
BACKGROUND: Acute-onset neurodegenerative diseases in older patients are rare clinical cases, especially when the degeneration only affects specific regions of the nervous system. Several neurological disorders have been described in which the degeneration of brain parenchyma originates from and/or primarily affects the brain stem. Clinical diagnosis in these patients, however, is often complicated due to a poor understanding of these diseases and their underlying mechanisms. CASE PRESENTATION: In this manuscript we report on a 73-year-old female who had experienced a sudden onset of complex neurological symptoms that progressively worsened over a period of 2 years...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27999666/beclin-1-mediated-autophagy-may-be-involved-in-the-elderly-cognitive-and-affective-disorders-in-streptozotocin-induced-diabetic-mice
#12
Zhu-Fei Guan, Xiu-Ling Zhou, Xiao-Ming Zhang, Yu Zhang, Yan-Mei Wang, Qi-Lin Guo, Gang Ji, Guo-Feng Wu, Na-Na Wang, Hao Yang, Zhong-Yu Yu, Hou-Guang Zhou, Jing-Chun Guo, Ying-Chao Liu
BACKGROUND: Diabetes is the most common metabolic disease with many chronic complications, and cognitive disorders are one of the common complications in patients with diabetes. Previous studies have showed that autophagy played important roles in the progression of metabolic syndrome, diabetes and other diseases. So we investigated whether aged diabetic mice are prone to be associated with the cognitive and affective disorders and whether Beclin-1-mediated autophagy might be involved in thepahological process...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27933142/salidroside-reduces-tau-hyperphosphorylation-via-up-regulating-gsk-3%C3%AE-phosphorylation-in-a-tau-transgenic-drosophila-model-of-alzheimer-s-disease
#13
Bei Zhang, Qiongqiong Li, Xingkun Chu, Suya Sun, Shengdi Chen
BACKGROUND: Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe treatment against AD. Salidroside (Sal) is the main effective component of Rhodiola rosea L., which has several pharmacological activities. The objective of this study was to investigate the efficacy of Sal in the treatment of AD transgenic Drosophila and the associated mechanisms...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27891223/is-apoe-%C3%A9-4-a-good-biomarker-for-amyloid-pathology-in-late-onset-alzheimer-s-disease
#14
REVIEW
Maowen Ba, Min Kong, Xiaofeng Li, Kok Pin Ng, Pedro Rosa-Neto, Serge Gauthier
Amyloid plaques are pathological hallmarks of Alzheimer's Disease (AD) and biomarkers such as cerebrospinal fluid (CSF) β-amyloid 1-42 (Aβ1-42) and amyloid positron emission tomographic (PET) imaging are important in diagnosing amyloid pathology in vivo. ɛ4 allele of the Apolipoprotein E gene (ApoE ɛ 4), which is a major genetic risk factor for late onset AD, is an important genetic biomarker for AD pathophysiology. It has been shown that ApoE ɛ 4 is involved in Aβ deposition and formation of amyloid plaques...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27822367/dysregulation-of-autophagy-and-mitochondrial-function-in-parkinson-s-disease
#15
REVIEW
Bao Wang, Neeta Abraham, Guodong Gao, Qian Yang
Parkinson's disease (PD) is the second most common neurodegenerative disease. Increasing evidence supports that dysregulation of autophagy and mitochondrial function are closely related with PD pathogenesis. In this review, we briefly summarized autophagy pathway, which consists of macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). Then, we discussed the involvement of mitochondrial dysfunction in PD pathogenesis. We specifically reviewed the recent developments in the relationship among several PD related genes, autophagy and mitochondrial dysfunction, followed by the therapeutic implications of these pathways...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27800157/the-study-of-brain-functional-connectivity-in-parkinson-s-disease
#16
REVIEW
Lin-Lin Gao, Tao Wu
Parkinson's disease (PD) is a neurodegenerative disorder primarily affecting the aging population. The neurophysiological mechanisms underlying parkinsonian symptoms remain unclear. PD affects extensive neural networks and a more thorough understanding of network disruption will help bridge the gap between known pathological changes and observed clinical presentations in PD. Development of neuroimaging techniques, especially functional magnetic resonance imaging, allows for detection of the functional connectivity of neural networks in patients with PD...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27761236/utility-of-susceptibility-weighted-imaging-in-parkinson-s-disease-and-atypical-parkinsonian-disorders
#17
Zhibin Wang, Xiao-Guang Luo, Chao Gao
In the clinic, the diagnosis of Parkinson's disease (PD) largely depends on clinicians' experience. When the diagnosis is made, approximately 80% of dopaminergic cells in the substantia nigra (SN) have been lost. Additionally, it is rather challenging to differentiate PD from atypical parkinsonian disorders (APD). Clinially-available 3T conventional MRI contributes little to solve these problems. The pathologic alterations of parkinsonism show abnormal brain iron deposition, and therefore susceptibility-weighted imaging (SWI), which is sensitive to iron concentration, has been applied to find iron-related lesions for the diagnosis and differentiation of PD in recent decades...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27570618/the-biomarkers-of-immune-dysregulation-and-inflammation-response-in-parkinson-disease
#18
REVIEW
Li Chen, Mingshu Mo, Guangning Li, Luan Cen, Lei Wei, Yousheng Xiao, Xiang Chen, Shaomin Li, Xinling Yang, Shaogang Qu, Pingyi Xu
Parkinson's disease (PD) is referring to the multi-systemic α-synucleinopathy with Lewy bodies deposited in midbrain. In ageing, the environmental and genetic factors work together and overactive major histocompatibility complex pathway to regulate immune reactions in central nerve system which resulting in neural degeneration, especially in dopaminergic neurons. As a series of biomarkers, the human leukocyte antigen genes with its related proteomics play cortical roles on the antigen presentation of major histocompatibility complex molecules to stimulate the differentiation of T lymphocytes and i-proteasome activities under their immune response to the PD-related environmental alteration and genetic variation...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27547386/the-predictive-value-of-ss-16-in-clinically-diagnosed-parkinson-s-disease-patients-comparison-with-99m-tc-trodat-1-spect-scans
#19
Wenyan Kang, Fangyi Dong, Dunhui Li, Thomas J Quinn, Shengdi Chen, Jun Liu
BACKGROUND: Dopamine transporter based imaging has high diagnostic performance in distinguishing patients with Parkinson's disease (PD) from patients with non-Parkinsonian syndromes. Our previous study indicated that the "Sniffin' Sticks" odor identification test (SS-16) acts as a valid instrument for olfactory assessment in Chinese PD patients. The aim of the study was to compare the efficacy of the two methods in diagnosing PD. METHODS: Fifty-two PD patients were involved in this study and underwent single photon emission computed tomography (SPECT) imaging using the labeled dopamine transporter radiotracer (99m)Tc-TRODAT-1 to assess nigrostriatal dopaminergic function...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27453777/mitochondrial-dysfunction-in-parkinson-s-disease
#20
REVIEW
Qingsong Hu, Guanghui Wang
Parkinson's disease (PD) is the second most common neurodegenerative disease, which is characterized by loss of dopaminergic (DA) neurons in the substantia nigra pars compacta and the formation of Lewy bodies and Lewy neurites in surviving DA neurons in most cases. Although the cause of PD is still unclear, the remarkable advances have been made in understanding the possible causative mechanisms of PD pathogenesis. Numerous studies showed that dysfunction of mitochondria may play key roles in DA neuronal loss...
2016: Translational Neurodegeneration
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