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https://www.readbyqxmd.com/read/28938641/potential-independent-action-of-sigma-receptor-ligands-through-inhibition-of-the-kv2-1-channel
#1
Xinying Liu, Yingmei Fu, Huan Yang, Timur Mavlyutov, Jun Li, Christopher R McCurdy, Lian-Wang Guo, Bikash R Pattnaik
The sigma-1 receptor (σ1-R) and sigma-2 receptor (σ2-R) are potential drug targets for treatment of cancer, pain, depression, retinal degeneration and other neuronal diseases. Previous reports show that sigma-1 receptor modulates the activities of multiple channels. We are interested in possible sigma receptor modulation of Kv2.1, a K(+) channel abundant in retinal photoreceptors. We tested the effect of established sigma receptor ligands on Kv2.1 channels which were stably expressed in HEK293 cells. Surprisingly, σ1-R antagonists inhibited Kv2...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938009/altering-neuronal-excitability-to-preserve-network-connectivity-in-a-computational-model-of-alzheimer-s-disease
#2
Willem de Haan, Elisabeth C W van Straaten, Alida A Gouw, Cornelis J Stam
Neuronal hyperactivity and hyperexcitability of the cerebral cortex and hippocampal region is an increasingly observed phenomenon in preclinical Alzheimer's disease (AD). In later stages, oscillatory slowing and loss of functional connectivity are ubiquitous. Recent evidence suggests that neuronal dynamics have a prominent role in AD pathophysiology, making it a potentially interesting therapeutic target. However, although neuronal activity can be manipulated by various (non-)pharmacological means, intervening in a highly integrated system that depends on complex dynamics can produce counterintuitive and adverse effects...
September 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28936769/nlrp3-inflammasome-activation-in-a-transgenic-amyotrophic-lateral-sclerosis-model
#3
Agnese Gugliandolo, Sabrina Giacoppo, Placido Bramanti, Emanuela Mazzon
Amyotrophic lateral sclerosis (ALS) is a disabling progressive disease characterized by the degeneration of motor neurons, leading to muscle atrophy and paralysis. The majority of cases are sporadic, but also a familiar form of ALS exists, and some genes causative of the pathology were found. In particular, mutations in superoxide dismutase 1 (SOD1) were found in 20% of familiar cases. It is known that neuroinflammation plays a pivotal role in several neurodegenerative disorders, including ALS. Inflammasomes are protein complexes that induce inflammation in response to various stimuli, involved also in neuroinflammation...
September 21, 2017: Inflammation
https://www.readbyqxmd.com/read/28936761/biomarkers-for-parkinson-s-disease-recent-advancement
#4
REVIEW
Sharvari Lotankar, Kedar S Prabhavalkar, Lokesh K Bhatt
As a multi-factorial degenerative disease, Parkinson's disease (PD) leads to tremor, gait rigidity, and hypokinesia, thus hampering normal living. As this disease is usually detected in the later stages when neurons have degenerated completely, cure is on hold, ultimately leading to death due to the lack of early diagnostic techniques. Thus, biomarkers are required to detect the disease in the early stages when prevention is possible. Various biomarkers providing early diagnosis of the disease include those of imaging, cerebrospinal fluid, oxidative stress, neuroprotection, and inflammation...
September 21, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28934388/loss-of-slc25a46-causes-neurodegeneration-by-affecting-mitochondrial-dynamics-and-energy-production-in-mice
#5
Zhuo Li, Yanyan Peng, Robert B Hufnagel, Yueh-Chiang Hu, Chuntao Zhao, Luis F Queme, Zaza Khuchua, Ashley M Driver, Fei Dong, Q Richard Lu, Diana M Lindquist, Michael P Jankowski, Rolf W Stottmann, Winston W Y Kao, Taosheng Huang
Recently, we identified biallelic mutations of SLC25A46 in patients with multiple neuropathies. Functional studies revealed that SLC25A46 may play an important role in mitochondrial dynamics by mediating mitochondrial fission. However, the cellular basis and pathogenic mechanism of the SLC25A46-related neuropathies are not fully understood. Thus, we generated a Slc25a46 knock-out mouse model. Mice lacking SLC25A46 displayed severe ataxia, mainly caused by degeneration of Purkinje cells. Increased numbers of small, unmyelinated and degenerated optic nerves as well as loss of retinal ganglion cells indicated optic atrophy...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934387/mutations-in-tgm6-induce-the-unfolded-protein-response-in-sca35
#6
Debasmita Tripathy, Beatrice Vignoli, Nandini Ramesh, Maria Jose Polanco, Marie Coutelier, Christopher D Stephen, Marco Canossa, Marie-Lorraine Monin, Pascale Aeschlimann, Shannon Turberville, Daniel Aeschlimann, Jeremy D Schmahmann, Marios Hadjivassiliou, Alexandra Durr, Udai B Pandey, Maria Pennuto, Manuela Basso
Spinocerebellar ataxia type 35 (SCA35) is a rare autosomal-dominant neurodegenerative disease caused by mutations in the TGM6 gene, which codes for transglutaminase 6 (TG6). Mutations in TG6 induce cerebellar degeneration by an unknown mechanism. We identified seven patients bearing new mutations in TGM6. To gain insights into the molecular basis of mutant TG6-induced neurotoxicity, we analyzed all the seven new TG6 mutants and the five TG6 mutants previously linked to SCA35. We found that the wild-type (TG6-WT) protein mainly localized to the nucleus and perinuclear area, whereas five TG6 mutations showed nuclear depletion, increased accumulation in the perinuclear area, insolubility and loss of enzymatic function...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28933786/pink1-interacts-with-%C3%AE-synuclein-and-abrogates-%C3%AE-synuclein-induced-neurotoxicity-by-activating-autophagy
#7
Jia Liu, Xue Wang, Yongquan Lu, Chunli Duan, Ge Gao, Lingling Lu, Hui Yang
Parkinson's disease (PD) is one of the most common neurodegenerative diseases, characterized by degeneration of dopaminergic neurons in the substantia nigra. α-synuclein (α-syn) and PTEN-induced putative kinase (PINK)1 are two critical proteins associated with the pathogenesis of PD. α-syn induces mitochondrial deficits and apoptosis, PINK1 was found to alleviate α-syn-induced toxicity, but the mechanistic details remain obscure. Here, we show that PINK1 interacts with α-syn mainly in the cytoplasm, where it initiates autophagy...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28933223/genetic-and-histological-alterations-reveal-key-role-of-prostaglandin-synthase-and-cyclooxygenase-1-and-2-in-traumatic-brain-injury-induced-neuroinflammation-in-the-cerebral-cortex-of-rats-exposed-to-moderate-fluid-percussion-injury
#8
Hideki Shojo, Cesario V Borlongan, Tadashi Mabuchi
After the initial insult in traumatic brain injury (TBI), secondary neurodegeneration occurs that is intimately associated with neuroinflammation. Prostaglandin (PG) synthases and cyclooxygenase (COX) 1 and 2 may contribute to inflammation in the brain. Temporal and spatial expression features of PG and COX1 and 2 following trauma may guide the development of antineuroinflammation strategies. Here, we examined PG synthase signaling and COX1 and 2 gene expression levels and COX-1- and 2-positive cell types and their temporal localization in TBI-induced brain in an effort to reveal their participation in the disease's evolving neuroinflammation...
July 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28931876/evidence-that-ca3-is-underling-the-comorbidity-between-pain-and-depression-and-the-co-curation-by-wu-tou-decoction-in-neuropathic-pain
#9
Chunyan Zhu, Qionghong Xu, Chao Wang, Zhiyun Mao, Na Lin
In neuropathic pain (NP), the atrophy of hippocampus contributes to the comorbidity between pain, depression and the cognitive deficits. However, the exact mechanism underling the comorbidity, the effective control of the degenerations in hippocampus and the remission of the accompanied depressive symptoms are still lacking. Wu-Tou decoction (WTD) has been prescribed for inflammatory pain for thousands of years. In this study, we manifested the effects of WTD on the pain, depression and anxiety co-curative symptoms of NP...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931760/inflammation-oxidative-stress-and-glial-cell-activation-characterize-stellate-ganglia-from-humans-with-electrical-storm
#10
Olujimi A Ajijola, Donald B Hoover, Thomas M Simerly, T Christopher Brown, Jane Yanagawa, Reshma M Biniwale, Jay M Lee, Ali Sadeghi, Negar Khanlou, Jeffrey L Ardell, Kalyanam Shivkumar
BACKGROUND: Neuronal remodeling in human heart disease is not well understood. METHODS: Stellate ganglia from patients with cardiomyopathy (CMY) and refractory ventricular arrhythmias undergoing cardiac sympathetic denervation (n = 8), and from organ donors with normal hearts (n = 8) collected at the time of organ procurement were compared. Clinical data on all subjects were reviewed. Electron microscopy (EM), histologic, and immunohistochemical assessments of neurotransmitter profiles, glial activation and distribution, and lipofuscin deposition, a marker of oxidative stress, were quantified...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931570/mitochondrial-dna-double-strand-breaks-in-oligodendrocytes-cause-demyelination-axonal-injury-and-cns-inflammation
#11
Pernille M Madsen, Milena Pinto, Shreyans Patel, Stephanie McCarthy, Han Gao, Mehran Taherian, Shaffiat Karmally, Claudia V Pereira, Galina Dvoriantchikova, Dmitry Ivanov, Kenji F Tanaka, Carlos T Moraes, Roberta Brambilla
Mitochondrial dysfunction has been implicated in the pathophysiology of neurodegenerative disorders, including multiple sclerosis (MS). To date, the investigation of mitochondrial dysfunction in MS has focused exclusively on neurons, with no studies exploring whether dysregulation of mitochondrial bioenergetics and/or genetics in oligodendrocytes might be associated with the etiopathogenesis of MS and other demyelinating syndromes. To address this question, we established a mouse model where mitochondrial DNA (mtDNA) double-strand breaks (DSB) were specifically induced in myelinating oligodendrocytes (PLP:mtPstI mice) by expressing a mitochondrial-targeted endonuclease, mtPstI, starting at 3 weeks of age...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28931463/severe-streptomycin-ototoxicity-in-the-mouse-utricle-leads-to-a-flat-epithelium-but-the-peripheral-neural-degeneration-is-delayed
#12
Guo-Peng Wang, Ishani Basu, Lisa A Beyer, Hiu Tung Wong, Donald L Swiderski, Shu-Sheng Gong, Yehoash Raphael
The damaged vestibular sensory epithelium of mammals has a limited capacity for spontaneous hair cell regeneration, which largely depends on the transdifferentiation of surviving supporting cells. Little is known about the response of vestibular supporting cells to a severe insult. In the present study, we evaluated the impact of a severe ototoxic insult on the histology of utricular supporting cells and the changes in innervation that ensued. We infused a high dose of streptomycin into the mouse posterior semicircular canal to induce a severe lesion in the utricle...
September 11, 2017: Hearing Research
https://www.readbyqxmd.com/read/28930688/the-heterochronic-gene-lin-14-controls-axonal-degeneration-in-c-%C3%A2-elegans-neurons
#13
Fiona K Ritchie, Rhianna Knable, Justin Chaplin, Rhiannon Gursanscky, Maria Gallegos, Brent Neumann, Massimo A Hilliard
The disproportionate length of an axon makes its structural and functional maintenance a major task for a neuron. The heterochronic gene lin-14 has previously been implicated in regulating the timing of key developmental events in the nematode C. elegans. Here, we report that LIN-14 is critical for maintaining neuronal integrity. Animals lacking lin-14 display axonal degeneration and guidance errors in both sensory and motor neurons. We demonstrate that LIN-14 functions both cell autonomously within the neuron and non-cell autonomously in the surrounding tissue, and we show that interaction between the axon and its surrounding tissue is essential for the preservation of axonal structure...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28929759/selective-inhibitors-of-dual-leucine-zipper-kinase-dlk-map3k12-with-activity-in-a-model-of-alzheimer-s-disease
#14
Snahel Patel, William J Meilandt, Rebecca I Erickson, Jinhua Chen, Gauri Deshmukh, Anthony A Estrada, Reina N Fuji, Paul Gibbons, Amy Gustafson, Seth F Harris, Jose Imperio, Wendy Liu, Xingrong Liu, Yichin Liu, Joseph P Lyssikatos, Changyou Ma, Jianping Yin, Joseph W Lewcock, Michael Siu
Significant data exists to suggest that dual leucine zipper kinase (DLK, MAP3K12) is a conserved regulator of neuronal degeneration following neuronal injury and in chronic neurodegenerative disease. Consequently, there is considerable interest in the identification of DLK inhibitors with a profile compatible with development for these indications. Herein, we use structure-based drug design combined with a focus on CNS drug-like properties to generate compounds with superior kinase selectivity and metabolic stability as compared to previously disclosed DLK inhibitors...
September 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28929183/altered-neurofilament-protein-expression-in-the-lateral-vestibular-nucleus-in-parkinson-s-disease
#15
Thomas P Wellings, Alan M Brichta, Rebecca Lim
A major cause of morbidity in Parkinson's disease (PD) is postural instability. The neuropathology underlying postural instability is unknown. Postural control is mediated by Deiters' neurons of the lateral vestibular nucleus (LVN), which are the brainstem origin of descending vestibulospinal reflexes. Deiters' neurons express the cytostructural protein, non-phosphorylated neurofilament protein (NPNFP). In PD, reduced expression of NPNFP in substantia nigra (SN) neurons is believed to contribute to dysfunction...
September 19, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28928628/axonal-degeneration-during-aging-and-its-functional-role-in-neurodegenerative-disorders
#16
REVIEW
Natalia Salvadores, Mario Sanhueza, Patricio Manque, Felipe A Court
Aging constitutes the main risk factor for the development of neurodegenerative diseases. This represents a major health issue worldwide that is only expected to escalate due to the ever-increasing life expectancy of the population. Interestingly, axonal degeneration, which occurs at early stages of neurodegenerative disorders (ND) such as Alzheimer's disease, Amyotrophic lateral sclerosis, and Parkinson's disease, also takes place as a consequence of normal aging. Moreover, the alteration of several cellular processes such as proteostasis, response to cellular stress and mitochondrial homeostasis, which have been described to occur in the aging brain, can also contribute to axonal pathology...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28926781/a-leukomyeloencephalopathy-of-unknown-origin-in-an-azawakh-dog
#17
Maria Teresa Mandara, Alice Reginato, Federica Balducci, Marco Bernardini
A diffuse bilaterally symmetrical leukomyeloencephalopathy was observed in a 6-year-old male Azawakh dog showing a slowly progressive ataxia of six months duration associated with sensory disorders. Severe bilaterally symmetrical demyelination and vacuolisation were confined to the dorsal columns along the entire spinal cord with a minor axonal degeneration. The main changes of myelin sheaths consisted in splitting and intramyelin vacuolization. Naked axons were scattered in a network of astrocytic processes and collagen fibres...
September 5, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28926646/vascular-hypoperfusion-in-acute-optic-neuritis-is-a-potentially-new-neurovascular-model-for-demyelinating-diseases
#18
Ta-Ching Chen, Chao-Yuan Yeh, Chao-Wen Lin, Chung-May Yang, Chang-Hao Yang, I-Hung Lin, Pao-Yang Chen, Jung-Yu Cheng, Fung-Rong Hu
PURPOSE: Optic neuritis is highly correlated with multiple sclerosis and is a major cause of acute visual loss and long-term neuronal degeneration. Primary cerebral hypoperfusion has been reported in brain demyelinating diseases. This study investigated whether peripapillary perfusion is changed in patients with acute optic neuritis (AON). METHODS: This three-year cohort study was conducted from September 1 2012, to August 31, 2015. Two hundred and forty-one patients with non-glaucomatous acute optic neuropathy were screened, and 42 non-highly myopic patients who had suffered their first episode of unilaterally idiopathic AON were studied...
2017: PloS One
https://www.readbyqxmd.com/read/28925478/effect-of-vegf-on-neuronal-degeneration-and-interaction-between-alzheimer-s-disease-biomarkers
#19
H-C Yuan, C-W Jiang, L-Y Hou, Y-B Lv, X-Z Feng, L-F Guo, G Sun, K Liu, Y-J Liu, B Xu, C-Y Wang
No abstract text is available yet for this article.
August 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28923480/impact-of-morphine-on-the-expression-of-insulin-receptor-and-protein-levels-of-insulin-igfs-in-rat-neural-stem-cells
#20
Sadegh Salarinasab, AliReza Nourazarian, Masoud Nikanfar, Nima Abdyazdani, Masoumeh Kazemi, Navid Feizy, Reza Rahbarghazi
Alzheimer's disease is correlated with neuronal degeneration and loss of neuronal precursors in different parts of the brain. It has been found disturbance in the homeostasis neural stem cells (NSCs) can cause neurodegeneration. Morphine, an analgesic agent, can disrupt the dynamic and normal state of NSCs. However, more investigations are required to clearly address underlying mechanisms. The current experiment aimed to investigate the effects of morphine on the cell distribution of insulin factor and receptor and insulin-like growth factors (IGF1, IGF2) in NSCs...
September 15, 2017: Neuroscience Letters
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