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Neurodegenerative disorder

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https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#1
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28210978/future-directions-in-imaging-neurodegeneration
#2
REVIEW
Joseph C Masdeu
Neuroimaging comprises a powerful set of instruments to diagnose various neurodegenerative disorders, clarifies their neurobiology, and monitors their treatment. Magnetic resonance imaging depicts volume changes, as well as abnormalities in functional and structural connectivity. Positron emission tomography (PET) allows for the quantification of regional cerebral metabolism, characteristically altered in Alzheimer's disease, amyotrophic lateral sclerosis, diffuse Lewy-body disease, and the frontotemporal dementias...
January 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28210976/regenerative-medicine-for-parkinson-s-disease-using-differentiated-nerve-cells-derived-from-human-buccal-fat-pad-stem-cells
#3
Haruka Takahashi, Hiroshi Ishikawa, Akira Tanaka
The purpose of this study was to evaluate the utility of human adipose stem cells derived from the buccal fat pad (hBFP-ASCs) for nerve regeneration. Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons. PD is a candidate disease for cell replacement therapy because it has no fundamental therapeutic methods. We examined the properties of neural-related cells induced from hBFP-ASCs as a cell source for PD treatment. hBFP-ASCs were cultured in neurogenic differentiation medium for about 2 weeks...
February 16, 2017: Human Cell
https://www.readbyqxmd.com/read/28210876/effect-of-hyperhomocysteinemia-on-redox-balance-and-redox-defence-enzymes-in-ischemia-reperfusion-injury-and-or-after-ischemic-preconditioning-in-rats
#4
Martin Petráš, Anna Drgová, Mária Kovalská, Zuzana Tatarková, Barbara Tóthová, Oľga Križanová, Ján Lehotský
Increased level of homocysteine (hHcy) in plasma is an accompanying phenomenon of many diseases, including a brain stroke. This study determines whether hyperhomocysteinemia (which is a risk factor of brain ischemia) itself or in combination with ischemic preconditioning affects the ischemia-induced neurodegenerative changes, generation of reactive oxygen species (ROS), lipoperoxidation, protein oxidation, and activity of antioxidant enzymes in the rat brain cortex. The hHcy was induced by subcutaneous administration of homocysteine (0...
February 16, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28210207/cannabinoid-receptor-2-signaling-in-neurodegenerative-disorders-from-pathogenesis-to-a-promising-therapeutic-target
#5
REVIEW
Tommaso Cassano, Silvio Calcagnini, Lorenzo Pace, Federico De Marco, Adele Romano, Silvana Gaetani
As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28209987/targeting-phospholipase-d-in-cancer-infection-and-neurodegenerative-disorders
#6
REVIEW
H Alex Brown, Paul G Thomas, Craig W Lindsley
Lipid second messengers have essential roles in cellular function and contribute to the molecular mechanisms that underlie inflammation, malignant transformation, invasiveness, neurodegenerative disorders, and infectious and other pathophysiological processes. The phospholipase D (PLD) isoenzymes PLD1 and PLD2 are one of the major sources of signal-activated phosphatidic acid (PtdOH) generation downstream of a variety of cell-surface receptors, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and integrins...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28208878/a-study-of-medication-compliance-in-geriatric-patients-with-chronic-illnesses-at-a-tertiary-care-hospital
#7
R Shruthi, R Jyothi, H P Pundarikaksha, G N Nagesh, T J Tushar
INTRODUCTION: Geriatric population is more prone for various chronic and recurrent illnesses like diabetes mellitus, hypertension, IHD, arthritic, neurodegenerative, gastrointestinal, ocular, genitourinary, respiratory disorders etc., which may require chronic medication with multiple drugs. Poor compliance in this age group accounts for medication wastage with increased cost of healthcare and substantial worsening of the disease with disability or death. Most of the human and economic costs associated with non adherence can be avoided by improving medication adherence...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28208707/gaitkeeper-a-system-for-measuring-canine-gait
#8
Cassim Ladha, Jack O'Sullivan, Zoe Belshaw, Lucy Asher
It is understood gait has the potential to be used as a window into neurodegenerative disorders, identify markers of subclinical pathology, inform diagnostic algorithms of disease progression and measure the efficacy of interventions. Dogs' gaits are frequently assessed in a veterinary setting to detect signs of lameness. Despite this, a reliable, affordable and objective method to assess lameness in dogs is lacking. Most described canine lameness assessments are subjective, unvalidated and at high risk of bias...
February 8, 2017: Sensors
https://www.readbyqxmd.com/read/28208696/valproate-attenuates-endoplasmic-reticulum-stress-induced-apoptosis-in-sh-sy5y-cells-via-the-akt-gsk3%C3%AE-signaling-pathway
#9
Zhengmao Li, Fenzan Wu, Xie Zhang, Yi Chai, Daqing Chen, Yuetao Yang, Kebin Xu, Jiayu Yin, Rui Li, Hongxue Shi, Zhouguang Wang, Xiaokun Li, Jian Xiao, Hongyu Zhang
Endoplasmic reticulum (ER) stress-induced apoptosis plays an important role in a range of neurological disorders, such as neurodegenerative diseases, spinal cord injury, and diabetic neuropathy. Valproate (VPA), a typical antiepileptic drug, is commonly used in the treatment of bipolar disorder and epilepsy. Recently, VPA has been reported to exert neurotrophic effects and promote neurite outgrowth, but its molecular mechanism is still unclear. In the present study, we investigated whether VPA inhibited ER stress and promoted neuroprotection and neuronal restoration in SH-SY5Y cells and in primary rat cortical neurons, respectively, upon exposure to thapsigargin (TG)...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208663/endoplasmic-reticulum-er-stress-and-endocrine-disorders
#10
REVIEW
Daisuke Ariyasu, Hiderou Yoshida, Yukihiro Hasegawa
The endoplasmic reticulum (ER) is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the "unfolded protein response" (UPR), which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress...
February 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208618/the-function-of-the-mitochondrial-calcium-uniporter-in-neurodegenerative-disorders
#11
REVIEW
Yajin Liao, Yuan Dong, Jinbo Cheng
The mitochondrial calcium uniporter (MCU)-a calcium uniporter on the inner membrane of mitochondria-controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208059/designer-protein-disaggregases-to-counter-neurodegenerative-disease
#12
REVIEW
James Shorter
Protein misfolding and aggregation unify several devastating neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. There are no effective therapeutics for these disorders and none that target the reversal of the aberrant protein misfolding and aggregation that cause disease. Here, I showcase important advances to define, engineer, and apply protein disaggregases to mitigate deleterious protein misfolding and counter neurodegeneration. I focus on two exogenous protein disaggregases, Hsp104 from yeast and gene 3 protein from bacteriophages, as well as endogenous human protein disaggregases, including: (a) Hsp110, Hsp70, Hsp40, and small heat-shock proteins; (b) HtrA1; and (c) NMNAT2 and Hsp90...
February 13, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28206745/atomistic-molecular-dynamics-simulations-of-mitochondrial-dna-polymerase-gamma-novel-mechanisms-of-function-and-pathogenesis
#13
Liliya Euro, Outi Haapanen, Tomasz Rog, Ilpo Vattulainen, Anu Suomalainen, Vivek Sharma
DNA polymerase gamma (Pol γ) is a key component of the mitochondrial DNA replisome and an important cause of neurological diseases. Despite the availability of its crystal structures, the molecular mechanism of DNA replication, the switch between polymerase and exonuclease activities, the site of replisomal interactions and functional effects of patient mutations that do not affect direct catalysis have remained elusive. Here we report first atomistic classical molecular dynamics (MD) simulations of human Pol γ replicative complex...
February 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/28205624/the-small-molecule-auten-99-autophagy-enhancer-99-prevents-the-progression-of-neurodegenerative-symptoms
#14
Tibor Kovács, Viktor Billes, Marcell Komlós, Bernadette Hotzi, Anna Manzéger, Anna Tarnóci, Diána Papp, Fanni Szikszai, Janka Szinyákovics, Ákos Rácz, Béla Noszál, Szilvia Veszelka, Fruzsina R Walter, Mária A Deli, Laszlo Hackler, Robert Alfoldi, Orsolya Huzian, Laszlo G Puskas, Hanna Liliom, Krisztián Tárnok, Katalin Schlett, Adrienn Borsy, Ervin Welker, Attila L Kovács, Zsolt Pádár, Attila Erdős, Adam Legradi, Annamaria Bjelik, Károly Gulya, Balázs Gulyás, Tibor Vellai
Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205010/prion-specific-and-surrogate-csf-biomarkers-in-creutzfeldt-jakob-disease-diagnostic-accuracy-in-relation-to-molecular-subtypes-and-analysis-of-neuropathological-correlates-of-p-tau-and-a%C3%AE-42-levels
#15
Francesca Lattanzio, Samir Abu-Rumeileh, Alessia Franceschini, Hideaki Kai, Giulia Amore, Ilaria Poggiolini, Marcello Rossi, Simone Baiardi, Lynne McGuire, Anna Ladogana, Maurizio Pocchiari, Alison Green, Sabina Capellari, Piero Parchi
The differential diagnosis of Creutzfeldt-Jakob disease (CJD) from other, sometimes treatable, neurological disorders is challenging, owing to the wide phenotypic heterogeneity of the disease. Real-time quaking-induced prion conversion (RT-QuIC) is a novel ultrasensitive in vitro assay, which, at variance with surrogate neurodegenerative biomarker assays, specifically targets the pathological prion protein (PrP(Sc)). In the studies conducted to date in CJD, cerebrospinal fluid (CSF) RT-QuIC showed good diagnostic sensitivity (82-96%) and virtually full specificity...
February 15, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28204864/high-bioavailability-curcumin-an-anti-inflammatory-and-neurosupportive-bioactive-nutrient-for-neurodegenerative-diseases-characterized-by-chronic-neuroinflammation
#16
REVIEW
Faheem Ullah, Andy Liang, Alejandra Rangel, Erika Gyengesi, Garry Niedermayer, Gerald Münch
Neuroinflammation is a pathophysiological process present in a number of neurodegenerative disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, stroke, traumatic brain injury including chronic traumatic encephalopathy and other age-related CNS disorders. Although there is still much debate about the initial trigger for some of these neurodegenerative disorders, during the progression of disease, broad range anti-inflammatory drugs including cytokine suppressive anti-inflammatory drugs (CSAIDs) might be promising therapeutic options to limit neuroinflammation and improve the clinical outcome...
February 15, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28204825/morroniside-protects-sk-n-sh-human-neuroblastoma-cells-against-h2o2-induced-damage
#17
Jing-Xing Zhang, Rui Wang, Jin Xi, Lin Shen, An-You Zhu, Qi Qi, Qi-Yi Wang, Lun-Jun Zhang, Feng-Chao Wang, He-Zuo Lü, Jian-Guo Hu
Oxidative stress-induced cell injury has been linked to the pathogenesis of neurodegenerative disorders such as spinal cord injury, Parkinson's disease, and multiple sclerosis. Morroniside is an antioxidant derived from the Chinese herb Shan-Zhu-Yu. The present study investigated the neuroprotective effect of morroniside against hydrogen peroxide (H2O2)-induced cell death in SK-N-SH human neuroblastoma cells. H2O2 increased cell apoptosis, as determined by flow cytometry and Hoechst 33342 staining. This effect was reversed by pretreatment with morroniside at concentrations of 1-100 µM...
February 8, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203648/gene-regulatory-effects-of-disease-associated-variation-in-the-nrf2-network
#18
Sarah E Lacher, Matthew Slattery
Reactive oxygen species (ROS), which are both a natural byproduct of oxidative metabolism and an undesirable byproduct of many environmental stressors, can damage all classes of cellular macromolecules and promote diseases from cancer to neurodegeneration. The actions of ROS are mitigated by the transcription factor NRF2, which regulates expression of antioxidant genes via its interaction with cis-regulatory antioxidant response elements (AREs). However, despite the seemingly straightforward relationship between the opposing forces of ROS and NRF2, regulatory precision in the NRF2 network is essential...
December 2016: Curr Opin Toxicol
https://www.readbyqxmd.com/read/28203480/a-novel-immunosuppressor-5r-5-hydroxytriptolide-alleviates-movement-disorder-and-neuroinflammation-in-a-6-ohda-hemiparkinsonian-rat-model
#19
Ruijun Su, Min Sun, Wei Wang, Jianliang Zhang, Li Zhang, Junli Zhen, Yanjing Qian, Yan Zheng, Xiaomin Wang
Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases. Promising therapies for PD still need to be explored. Immune dysfunction has been found to be involved in PD pathogenesis. Here, a novel immunosuppressor, (5R)-5-hydroxytriptolide (LLDT8), was used to treat 6-hydroxydopamine (6-OHDA)-induced hemiparkinson rats. We found that oral administration of LLDT8 significantly alleviated apomorphine-induced rotations at a dose of 125 µg/kg, and improved performance in cylinder and rotarod tests at a lower dose of 31...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28203298/prolyl-isomerase-pin1-and-neurotrophins-a-loop-that-may-determine-the-fate-of-cells-in-cancer-and-neurodegeneration
#20
REVIEW
Francesco Angelucci, Jakub Hort
Increased survival, differentiation, and apoptotic death are common mechanisms relevant for both cancer and neurodegenerative diseases. Although these disorders are characterized by different manifestations, it appears that a common mechanism may be present which directs the fate of a cell to either degeneration or proliferation. There are two classes of proteins that have been extensively investigated in these diseases but their possible interaction during signal transduction has not been studied. Prolyl isomerase Pin1 is an enzyme which translates Ser/Thr-Pro phosphorylation into conformational changes able to modify the activities of its substrates...
January 2017: Therapeutic Advances in Medical Oncology
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