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https://www.readbyqxmd.com/read/28108584/astrocytic-transporters-in-alzheimer-s-disease
#1
REVIEW
Chris Ugbode, Yuhan Hu, Benjamin Whalley, Chris Peers, Marcus Rattray, Mark L Dallas
Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture...
February 1, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28108397/aav9-igf1-protects-tdp-25-cells-from-apoptosis-and-oxidative-stress-partly-via-up-regulating-the-expression-of-vegf-in-vitro
#2
Zhongyao Li, Weisong Duan, Can Cui, Yaling Liu, Chunyan Li, Yakun Liu
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease lacking of curable treatments to date. Adeno-associated virus (AAV) vectors make gene therapy an effective strategy in treating neurological disorders. Despite Kaspar and colleagues have showed that AAV-IGF1 delivery successfully prolonged the survival of SOD1G93A mice, whether IGF-1 act as a protective role in the TDP-43 mutant model still have not been reported. In this study, we proved that AAV9 vector mediated expression of human wild-type IGF-1 protected TDP-25 cells from apoptosis and oxidative stress...
January 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28108264/iron-accumulation-and-microglia-activation-contribute-to-substantia-nigra-hyperechogenicity-in-the-6-ohda-induced-rat-model-of-parkinson-s-disease
#3
Yaqin Zhu, Bao Wang, Kai Tao, Hengli Yang, Yixiao Wang, Tian Zhou, Yilin Yang, Lijun Yuan, Xi Liu, Yunyou Duan
INTRODUCTION: This study aims to explain the mechanisms for the formation of sonographic features of Parkinson's disease (PD) using a 6-hydroxydopamine (6-OHDA) rat model of PD. The iron chelator deferiprone (DFP) was used in the PD model rat to examine the relationship between iron and the echo signal. METHODS: Rat models were created using stereotactic injections of 6-OHDA. DFP was administered intragastrically. Transcranial sonography (TCS) was performed to observe the substantia nigra (SN) echo signal of the brain...
January 6, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28108258/downregulation-of-iduna-is-associated-with-aif-nuclear-translocation-in-neonatal-brain-after-hypoxia-ischemia
#4
Xiaoxia Jianhua Yang Cheng, Yubo Juan Gao Ding, Xinli Ni
In adult stroke models, the neuroprotective protein, Iduna, inhibits poly (ADP-ribose) polymerase-1 (PARP-1)-dependent cell death by decreasing apoptosis-inducing factor (AIF) nuclear translocation. Because the PARP1-dependent pathway and Iduna, which promotes AIF degradation, contribute to hypoxic-ischemic (HI) brain damage in the immature brain, we examined the relationship between Iduna expression and AIF nuclear translocation in the cerebral cortex of postnatal day 7 rats after HI. Ninety rats were divided into three groups: sham, 1-h hypoxia and 2-h hypoxia...
January 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28107862/neuroprotective-effect-of-spilanthes-acmella-murr-on-pesticide-induced-neuronal-cells-death
#5
Wilasinee Suwanjang, Bongkot Khongniam, Sujittra Srisung, Supaluk Prachayasittikul, Virapong Prachayasittikul
OBJECTIVE: To investigate protective effects of Spilanthes acmella (S. acmella) Murr. extracts against pesticide-induced neuronal cells death and to elucidate the underlying molecular mechanism in dopaminergic (SH-SY5Y) cells lines. METHODS: Cell viability of SH-SY5Y cells was studied by treating the cells with various concentration of pirimicarb for 24 h. Neuroprotective effect of S. acmella Murr. extracts was investigated by adding the plant extracts to the medium for 24 h prior to the incubation with 100 μM H2O2 or with pirimicarb for 24 h...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28106982/a-novel-iron-ii-preferring-dopamine-agonist-chelator-as-potential-symptomatic-and-neuroprotective-therapeutic-agent-for-parkinson-s-disease
#6
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy L Stemmler, Maarten E A Reith, Aloke K Dutta
Parkinson's disease (PD) is a progressive neurodegenerative disorder and development of disease-modifying treatment is still an unmet medical need. Considering the implication of free iron (II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-)-12 (D-607) as a multitarget-directed ligand against PD. Binding and functional assays at dopamine D2/D3 receptors indicate potent agonist activity of (-)-12. The molecule displayed an efficient preferential iron (II) chelation properties along with potent in vivo activity in a reserpinized PD animal model...
January 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28106854/the-effect-of-polyphenols-on-protein-degradation-pathways-implications-for-neuroprotection
#7
REVIEW
Parvana Hajieva
Human neurodegenerative diseases are accompanied by accumulation of heavily oxidized and aggregated proteins. However, the exact molecular reason is not fully elucidated yet. Insufficient cellular protein quality control is thought to play an important role in accumulating covalently oxidized misfolded proteins. Pharmacologically active polyphenols and their derivatives exhibit potential for preventive and therapeutic purposes against protein aggregation during neurodegeneration. Although these compounds act on various biochemical pathways, their role in stabilizing the protein degradation machinery at different stages may be an attractive therapeutical strategy to halt the accumulation of misfolded proteins...
January 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106827/neuroprotective-strategy-in-retinal-degeneration-suppressing-er-stress-induced-cell-death-via-inhibition-of-the-mtor-signal
#8
REVIEW
Bin Fan, Ying-Jian Sun, Shu-Yan Liu, Lin Che, Guang-Yu Li
The retina is a specialized sensory organ, which is essential for light detection and visual formation in the human eye. Inherited retinal degenerations are a heterogeneous group of eye diseases that can eventually cause permanent vision loss. UPR (unfolded protein response) and ER (endoplasmic reticulum) stress plays an important role in the pathological mechanism of retinal degenerative diseases. mTOR (the mammalian target of rapamycin) kinase, as a signaling hub, controls many cellular processes, covering protein synthesis, RNA translation, ER stress, and apoptosis...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106777/neuroprotection-by-caffeine-in-hyperoxia-induced-neonatal-brain-injury
#9
Stefanie Endesfelder, Ulrike Weichelt, Evelyn Strauß, Anja Schlör, Marco Sifringer, Till Scheuer, Christoph Bührer, Thomas Schmitz
Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term "oxygen radical disease of prematurity". Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106772/neuroprotective-and-anti-apoptotic-effects-of-csp-1103-in-primary-cortical-neurons-exposed-to-oxygen-and-glucose-deprivation
#10
Vanessa Porrini, Ilenia Sarnico, Marina Benarese, Caterina Branca, Mariana Mota, Annamaria Lanzillotta, Arianna Bellucci, Edoardo Parrella, Lara Faggi, Pierfranco Spano, Bruno Pietro Imbimbo, Marina Pizzi
CSP-1103 (formerly CHF5074) has been shown to reverse memory impairment and reduce amyloid plaque as well as inflammatory microglia activation in preclinical models of Alzheimer's disease. Moreover, it was found to improve cognition and reduce brain inflammation in patients with mild cognitive impairment. Recent evidence suggests that CSP-1103 acts through a single molecular target, the amyloid precursor protein intracellular domain (AICD), a transcriptional regulator implicated in inflammation and apoptosis...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106099/nesfatin-1-protects-dopaminergic-neurons-against-mpp-mptp-induced-neurotoxicity-through-the-c-raf-erk1-2-dependent-anti-apoptotic-pathway
#11
Xiao-Li Shen, Ning Song, Xi-Xun Du, Yong Li, Jun-Xia Xie, Hong Jiang
Several brain-gut peptides have been reported to have a close relationship with the central dopaminergic system; one such brain-gut peptide is nesfatin-1. Nesfatin-1 is a satiety peptide that is predominantly secreted by X/A-like endocrine cells in the gastric glands, where ghrelin is also secreted. We previously reported that ghrelin exerted neuroprotective effects on nigral dopaminergic neurons, which implied a role for ghrelin in Parkinson's disease (PD). In the present study, we aim to clarify whether nesfatin-1 has similar effects on dopaminergic neurons both in vivo and in vitro...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106097/lancl-proteins-are-not-involved-in-lanthionine-synthesis-in-mammals
#12
Chang He, Min Zeng, Debapriya Dutta, Tong Hee Koh, Jie Chen, Wilfred A van der Donk
LanC-like (LanCL) proteins are mammalian homologs of bacterial LanC enzymes, which catalyze the addition of the thiol of Cys to dehydrated Ser residues during the biosynthesis of lanthipeptides, a class of natural products formed by post-translational modification of precursor peptides. The functions of LanCL proteins are currently unclear. A recent proposal suggested that LanCL1 catalyzes the addition of the Cys of glutathione to protein- or peptide-bound dehydroalanine (Dha) to form lanthionine, analogous to the reaction catalyzed by LanC in bacteria...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105979/human-dental-pulp-stem-cells-are-more-effective-than-human-bone-marrow-derived-mesenchymal-stem-cells-in-cerebral-ischemic-injury
#13
Miyeoun Song, Jae-Hyung Lee, Jinhyun Bae, Youngmin Bu, Eun-Cheol Kim
We compared the therapeutic effects and mechanism of transplanted human dental pulp stem cells (hDPSCs) and human bonemarrow-derived mesenchymal stem cells (hMSCs) in a stroke model of rats and an <i>in vitro</i> ischemic model. Both hDPSCs- and hMSCs- intravenously injected rats 24&#8201;h after middle cerebral artery occlusion showed improved functional recovery and reduced infarct volume versus control rats, but the hDPSCs group showed greater reduction in infarct volume than hMSCs. The positive area for the endothelial cell marker was greater in the lesion boundary areas in the hDPSCs group than with hMSCs...
January 20, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28105567/effects-of-oleuropein-on-pentylenetetrazol-induced-seizures-in-mice-involvement-of-opioidergic-and-nitrergic-systems
#14
Nastaran Rahimi, Bahram Delfan, Nazgol Motamed-Gorji, Ahmad R Dehpour
Oleuropein, a well-known olive polyphenol, has been shown to mediate neuroprotection in Alzheimer's disease and cerebral ischemia. We investigated the effects of oleuropein on pentylenetetrazole (PTZ)-induced seizures in male NMRI mice, with diazepam as the standard drug. We also examined the possible involvement of opioidergic/nitrergic pathways in the probable effects of oleuropein. Intraperitoneal (i.p.) administration of different doses of oleuropein (10, 20 and 30 mg/kg) significantly increased the seizure threshold 60 min prior to induction of seizure, in a dose-dependent manner...
January 19, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28105520/type-1-diabetic-patients-with-peripheral-neuropathy-have-pan-enteric-prolongation-of-gastrointestinal-transit-times-and-an-altered-caecal-ph-profile
#15
Adam D Farmer, Anne Grave Pedersen, Birgitte Brock, Poul Erik Jakobsen, Jesper Karmisholt, Sahar D Mohammed, S Mark Scott, Asbjørn Mohr Drewes, Christina Brock
AIMS/HYPOTHESIS: We hypothesised that type 1 diabetic patients with established diabetic sensorimotor polyneuropathy (DSPN) would have segmental and/or pan-enteric dysmotility in comparison to healthy age-matched controls. We aimed to investigate the co-relationships between gastrointestinal function, degree of DSPN and clinical symptoms. METHODS: An observational comparison was made between 48 patients with DSPN (39 men, mean age 50 years, range 29-71 years), representing the baseline data of an ongoing clinical trial (representing a secondary analysis of baseline data collected from an ongoing double-blind randomised controlled trial investigating the neuroprotective effects of liraglutide) and 41 healthy participants (16 men, mean age 49 years, range 30-78) who underwent a standardised wireless motility capsule test to assess gastrointestinal transit...
January 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28104249/il-17-signalling-in-astrocytes-promotes-glutamate-excitotoxicity-indications-for-the-link-between-inflammatory-and-neurodegenerative-events-in-multiple-sclerosis
#16
Milos Kostic, Nikola Zivkovic, Ana Cvetanovic, Ivana Stojanovic, Miodrag Colic
OBJECTIVE: Th-17 cells have been exclusively referred to inflammatory events in multiple sclerosis (MS), while their importance in the development of glutamate excitotoxicity and the consequent neurodegeneration has been a completely unexplored concept. Accordingly, the objective of our study was to assess IL-17A effect on astrocyte ability to metabolize and release glutamate, considering that astrocytes had the central role in glutamate homeostasis. METHODS: By using primary rat astrocyte cultures, astrocyte ability to uptake glutamate was estimated by the alterations of glutamate transporters (GLAST and GLT-1) expression, whereas changes in glutamine synthetase expression were used to estimate the ability to metabolize glutamate...
January 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28103798/selenium-suppresses-glutamate-induced-cell-death-and-prevents-mitochondrial-morphological-dynamic-alterations-in-hippocampal-ht22-neuronal-cells
#17
Yan-Mei Ma, Gordon Ibeanu, Li-Yao Wang, Jian-Zhong Zhang, Yue Chang, Jian-Da Dong, P Andy Li, Li Jing
BACKGROUND: Previous studies have indicated that selenium supplementation may be beneficial in neuroprotection against glutamate-induced cell damage, in which mitochondrial dysfunction is considered a major pathogenic feature. However, the exact mechanisms by which selenium protects against glutamate-provoked mitochondrial perturbation remain ambiguous. In this study glutamate exposed murine hippocampal neuronal HT22 cell was used as a model to investigate the underlying mechanisms of selenium-dependent protection against mitochondria damage...
January 19, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28103118/park2-dependent-mitophagy-induced-by-acidic-postconditioning-protects-against-focal-cerebral-ischemia-and-extends-the-reperfusion-window
#18
Zhe Shen, Yanrong Zheng, Jiaying Wu, Ying Chen, Xiaoli Wu, Yiting Zhou, Yang Yuan, Shousheng Lu, Lei Jiang, Zhenghong Qin, Zhong Chen, Weiwei Hu, Xiangnan Zhang
Prompt reperfusion after cerebral ischemia is critical for neuronal survival. Any strategies that extend the limited reperfusion window will be of great importance. Acidic postconditioning (APC) is a mild acidosis treatment that involves inhaling CO2 during reperfusion following ischemia. APC attenuates ischemic brain injury although the underlying mechanisms have not been elucidated. Here we report that APC reinforces ischemia-reperfusion-induced mitophagy in middle cortical artery occlusion (MCAO)-treated mice, and in oxygen-glucose deprivation (OGD)-treated brain slices and neurons...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28102474/anti-amnestic-effect-of-curcumin-in-combination-with-donepezil-an-anticholinesterase-drug-involvement-of-cholinergic-system
#19
Ayodele Jacob Akinyemi, Ganiyu Oboh, Sunday Idowu Oyeleye, Opeyemi Ogunsuyi
Recently, combination therapy involving cholinesterase (ChE) inhibitor with other neuroprotective agents has shown better desirable effect in the management/prevention of dementia but limited information is available on their effect with dietary polyphenols. Hence, this study sought to assess the combined pretreatment effect of curcumin, the major polyphenolic compound of turmeric (Curcuma longa) rhizomes, with donepezil, a cholinesterase inhibitor, on cognitive function in scopolamine-induced memory impairment in rats...
January 19, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28101749/twenty-seven-years-of-cerebral-pyruvate-recycling
#20
Sebastián Cerdán
Cerebral pyruvate recycling is a metabolic pathway deriving carbon skeletons and reducing equivalents from mitochondrial oxaloacetate and malate, to the synthesis of mitochondrial and cytosolic pyruvate, lactate and alanine. The pathway allows both, to provide the tricarboxylic acid cycle with pyruvate molecules produced from alternative substrates to glucose and, to generate reducing equivalents necessary for the operation of NADPH requiring processes. At the cellular level, pyruvate recycling involves the activity of malic enzyme, or the combined activities of phosphoenolpyruvate carboxykinase and pyruvate kinase, as well as of those transporters of the inner mitochondrial membrane exchanging the corresponding intermediates...
January 18, 2017: Neurochemical Research
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