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parkinson's disease and endoplasmic reticulum stress

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https://www.readbyqxmd.com/read/28316566/blockade-of-ryrs-in-the-er-attenuates-6-ohda-induced-calcium-overload-cellular-hypo-excitability-and-apoptosis-in-dopaminergic-neurons
#1
Lu Huang, Ying Xue, DaYun Feng, RuiXin Yang, Tiejian Nie, Gang Zhu, Kai Tao, GuoDong Gao, Qian Yang
Calcium (Ca(2+)) dyshomeostasis induced by endoplasmic reticulum (ER) stress is an important molecular mechanism of selective dopaminergic (DA) neuron loss in Parkinson's disease (PD). Inositol 1,4,5-triphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), which are located on the ER surface, are the main endogenous Ca(2+) release channels and play crucial roles in regulating Ca(2+) homeostasis. However, the roles of these endogenous Ca(2+) release channels in PD and their effects on the function and survival of DA neurons remain unknown...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28315279/the-role-of-sigma-1-receptor-as-a-neuroprotective-target-in-glaucoma
#2
Barbara Mysona, Neil Kansara, Jing Zhao, Kathryn Bollinger
The role of sigma 1 receptor (S1R) in glaucoma is emerging as a promising field of study. Glaucoma is an optic neuropathy that shares common pathogenic mechanisms with other neurodegenerative diseases such as Alzheimer's and Parkinson's disease . S1R modulates multiple cellular functions associated with neurodegeneration . These include Ca(2+) ion homeostasis, endoplasmic reticulum (ER) and oxidative stress , survival signaling pathways, neurotrophin secretion, and glial activation. S1R may also have neurorestorative properties including enhancement of neuronal plasticity and neurite outgrowth...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28273718/mechanisms-of-parkinson-s-disease-related-proteins-in-mediating-secondary-brain-damage-after-cerebral-ischemia
#3
TaeHee Kim, Raghu Vemuganti
Both Parkinson's disease (PD) and stroke are debilitating conditions that result in neuronal death and loss of neurological functions. These two conditions predominantly affect aging populations with the deterioration of the quality of life for the patients themselves and a tremendous burden to families. While the neurodegeneration and symptomology of PD develop chronically over the years, post-stroke neuronal death and dysfunction develop rapidly in days. Despite the discrepancy in the pathophysiological time frame and severity, both conditions share common molecular mechanisms that include oxidative stress, mitochondrial dysfunction, inflammation, endoplasmic reticulum stress, and activation of various cell death pathways (apoptosis/necrosis/autophagy) that synergistically modulate the neuronal death...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28243526/bax-inhibitor-1-knockdown-phenotypes-are-suppressed-by-buffy-and-exacerbate-degeneration-in-a-drosophila-model-of-parkinson-disease
#4
P Githure M'Angale, Brian E Staveley
BACKGROUND: Bax inhibitor-1 (BI-1) is an evolutionarily conserved cytoprotective transmembrane protein that acts as a suppressor of Bax-induced apoptosis by regulation of endoplasmic reticulum stress-induced cell death. We knocked down BI-1 in the sensitive dopa decarboxylase (Ddc) expressing neurons of Drosophila melanogaster to investigate its neuroprotective functions. We additionally sought to rescue the BI-1-induced phenotypes by co-expression with the pro-survival Buffy and determined the effect of BI-1 knockdown on the neurodegenerative α-synuclein-induced Parkinson disease (PD) model...
2017: PeerJ
https://www.readbyqxmd.com/read/28193519/thiamine-deficiency-induces-endoplasmic-reticulum-stress-and-oxidative-stress-in-human-neurons-derived-from-induced-pluripotent-stem-cells
#5
Xin Wang, Mei Xu, Jacqueline A Frank, Zun-Ji Ke, Jia Luo
Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear...
April 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28131727/long-term-protective-effects-of-aav9-mesencephalic-astrocyte-derived-neurotrophic-factor-gene-transfer-in-parkinsonian-rats
#6
Fei Hao, Chun Yang, Sha-Sha Chen, Yan-Yan Wang, Wei Zhou, Qiang Hao, Tao Lu, Barry Hoffer, Li-Ru Zhao, Wei-Ming Duan, Qun-Yuan Xu
Intrastriatal injection of mesencephalic astrocyte-derived neurotrophic factor (MANF) protein has been shown to provide neuroprotective and neurorestorative effects in a 6-hydroxydopamine (6-OHDA) - lesioned rat model of Parkinson's disease. Here, we used an adeno-associated virus serotype 9 (AAV9) vector to deliver the human MANF (hMANF) gene into the rat striatum 10days after a 6-OHDA lesion to examine long-term effects of hMANF on nigral dopaminergic neurons and mechanisms underlying MANF neuroprotection...
January 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28116245/7-ketocholesterol-induces-apoptosis-of-mc3t3-e1-cells-associated-with-reactive-oxygen-species-generation-endoplasmic-reticulum-stress-and-caspase-3-7-dependent-pathway
#7
Yuta Sato, Noriko Ishihara, Daiji Nagayama, Atsuhito Saiki, Ichiro Tatsuno
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of bone fractures without reduction of bone mineral density. The cholesterol oxide 7-ketocholesterol (7KCHO) has been implicated in numerous diseases such as atherosclerosis, Alzheimer's disease, Parkinson's disease, cancer, age-related macular degeneration and T2DM. In the present study, 7KCHO decreased the viability of MC3T3-E1 cells, increased reactive oxygen species (ROS) production and apoptotic rate, and upregulated the caspase-3/7 pathway...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28087337/tunicamycin-impairs-olfactory-learning-and-synaptic-plasticity-in-the-olfactory-bulb
#8
Jia Tong, Fumino Okutani, Yoshihiro Murata, Mutsuo Taniguchi, Toshiharu Namba, Yu-Jie Wang, Hideto Kaba
Tunicamycin (TM) induces endoplasmic reticulum (ER) stress and inhibits N-glycosylation in cells. ER stress is associated with neuronal death in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, and most patients complain of the impairment of olfactory recognition. Here we examined the effects of TM on aversive olfactory learning and the underlying synaptic plasticity in the main olfactory bulb (MOB). Behavioral experiments demonstrated that the intrabulbar infusion of TM disabled aversive olfactory learning without affecting short-term memory...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28004277/tauroursodeoxycholic-bile-acid-arrests-axonal-degeneration-by-inhibiting-the-unfolded-protein-response-in-x-linked-adrenoleukodystrophy
#9
Nathalie Launay, Montserrat Ruiz, Laia Grau, Francisco J Ortega, Ekaterina V Ilieva, Juan José Martínez, Elena Galea, Isidre Ferrer, Erwin Knecht, Aurora Pujol, Stéphane Fourcade
The activation of the highly conserved unfolded protein response (UPR) is prominent in the pathogenesis of the most prevalent neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), which are classically characterized by an accumulation of aggregated or misfolded proteins. This activation is orchestrated by three endoplasmic reticulum (ER) stress sensors: PERK, ATF6 and IRE1. These sensors transduce signals that induce the expression of the UPR gene programme...
February 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/27939990/apomorphine-prevents-lps-induced-il-23-p19-mrna-expression-via-inhibition-of-jnk-and-atf4-in-hapi-cells
#10
Hirokazu Hara, Dai Kimoto, Miho Kajita, Chisato Takada, Tetsuro Kamiya, Tetsuo Adachi
Inflammation has been reported to be closely related to exaggeration of cerebral ischemia and neurodegenerative diseases. Microglia, resident immune cells in the central nervous system, can be activated in response to neuronal injury and produce proinflammatory cytokines, resulting in further aggravation of neuronal injury. Interleukin (IL)-23, which consists of p19 and IL-12 p40 subunits, has been shown to be involved in brain injury associated with neuroinflammation. Apomorphine (Apo), a nonselective dopamine receptor agonist, has been used for clinical therapy of Parkinson's disease...
December 9, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27866808/combined-beta-glucosylceramide-and-ambroxol-hydrochloride-in-patients-with-gaucher-related-parkinson-disease-from-clinical-observations-to-drug-development
#11
Yuval Ishay, Ari Zimran, Jeffrey Szer, Tama Dinur, Yaron Ilan, David Arkadir
Both patients with non-neuronopathic Gaucher disease (GD) and heterozygous GBA mutation carrier are at increased risk for Parkinson disease (PD). The risk for PD in these groups does not linearly increase with glucosylceramide (GC) accumulation or with acid β-glucocerebrosidase (GCase) activity. This observation, together with other clinical systemic observations raises the possibility that extra-cellular GC actually has beneficial, anti-inflammatory, properties. Based on this hypothesis, we suggest here that the administration of supplementary oral GC to GBA carriers at risk for PD may slow inflammatory-driven secondary neuronal death...
November 12, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27815720/the-role-of-endoplasmic-reticulum-stress-in-neurodegenerative-disease
#12
REVIEW
Chunchen Xiang, Yujia Wang, Han Zhang, Fang Han
The endoplasmic reticulum (ER) is an important organelle involved in cellular homeostasis and control of protein quality. Unfolded protein response (UPR) is a cellular response to ER stress and promotes cell survival. Severe or prolonged stress activates apoptosis signaling to trigger cell death. In mammals, the UPR is initiated by three major ER stress sensors, including inositol-requiring transmembrane kinase 1, double-stranded RNA-activated protein kinase-like ER kinase and activating transcription factor 6...
November 4, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27776889/a-new-target-for-parkinson-s-disease-small-molecule-serca-activator-cdn1163-ameliorates-dyskinesia-in-6-ohda-lesioned-rats
#13
Russell Dahl
Endoplasmic reticulum (ER) stress is intimately linked to Parkinson's disease (PD) pathophysiology. Disrupted intracellular calcium homeostasis is a major cause of the ER stress seen in dopaminergic neurons, leading to the cell death and subsequent loss of movement and coordination in patients. Dysfunctional calcium handling proteins play a major role in the promulgation of ER stress in PD. Specifically, compromised sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) has been identified as a major cause of ER stress and neuron loss in PD...
January 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27774335/n-acetylcysteine-in-combination-with-igf-1-enhances-neuroprotection-against-proteasome-dysfunction-induced-neurotoxicity-in-sh-sy5y-cells
#14
Benxu Cheng, Pinki Anand, Anxiu Kuang, Feroz Akhtar, Virginia L Scofield
Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson's disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells...
2016: Parkinson's Disease
https://www.readbyqxmd.com/read/27748814/neurotoxin-%C3%AE-%C3%A2-n%C3%A2-methylamino%C3%A2-l%C3%A2-alanine-induces-endoplasmic-reticulum-stress%C3%A2-mediated-neuronal-apoptosis
#15
Haiying Shen, Kiyoon Kim, Yoojung Oh, Kyung Sik Yoon, Hyung Hwan Baik, Sung Soo Kim, Joohun Ha, Insug Kang, Wonchae Choe
β-N-methylamino-L-alanine (BMAA) is a neurotoxin that is closely associated with the incidence of amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. In cultured neuronal cells, BMAA notably induces the upregulation of endoplasmic reticulum (ER) chaperons and activates the unfolded protein response (UPR) receptor pathways of protein kinase RNA‑like endoplasmic reticulum kinase, inositol‑requiring kinase 1 and transcription factor 6. The ER stress‑specific protein CCAAT/‑enhancer‑binding protein homologous protein (CHOP) affords pro‑apoptotic responses that cause mitochondrial damage and caspase activation...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27736935/chemical-compensation-of-mitochondrial-phospholipid-depletion-in-yeast-and-animal-models-of-parkinson-s-disease
#16
Shaoxiao Wang, Siyuan Zhang, Chuan Xu, Addie Barron, Floyd Galiano, Dhaval Patel, Yong Joo Lee, Guy A Caldwell, Kim A Caldwell, Stephan N Witt
We have been investigating the role that phosphatidylethanolamine (PE) and phosphatidylcholine (PC) content plays in modulating the solubility of the Parkinson's disease protein alpha-synuclein (α-syn) using Saccharomyces cerevisiae and Caenorhabditis elegans. One enzyme that synthesizes PE is the conserved enzyme phosphatidylserine decarboxylase (Psd1/yeast; PSD-1/worms), which is lodged in the inner mitochondrial membrane. We previously found that decreasing the level of PE due to knockdown of Psd1/psd-1 affects the homeostasis of α-syn in vivo...
2016: PloS One
https://www.readbyqxmd.com/read/27714635/mitochondria-associated-membranes-mams-overview-and-its-role-in-parkinson-s-disease
#17
M Rodríguez-Arribas, S M S Yakhine-Diop, J M Bravo-San Pedro, P Gómez-Suaga, R Gómez-Sánchez, G Martínez-Chacón, J M Fuentes, R A González-Polo, M Niso-Santano
Mitochondria-associated membranes (MAMs) are structures that regulate physiological functions between endoplasmic reticulum (ER) and mitochondria in order to maintain calcium signaling and mitochondrial biogenesis. Several proteins located in MAMs, including those encoded by PARK genes and some of neurodegeneration-related proteins (huntingtin, presenilin, etc.), ensure this regulation. In this regard, MAM alteration is associated with neurodegenerative diseases such as Parkinson's (PD), Alzheimer's (AD), and Huntington's diseases (HD) and contributes to the appearance of the pathogenesis features, i...
October 6, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27660269/er-stress-induced-by-tunicamycin-triggers-%C3%AE-synuclein-oligomerization-dopaminergic-neurons-death-and-locomotor-impairment-a-new-model-of-parkinson-s-disease
#18
Valentín Cóppola-Segovia, Clarissa Cavarsan, Flavia G Maia, Anete C Ferraz, Lia S Nakao, Marcelo Ms Lima, Silvio M Zanata
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons of the substantia nigra pars compacta (SNpc), leading to the major clinical abnormalities that characterize this disease. Although PD's etiology is unknown, α-synuclein aggregation plays a pivotal role in PD pathogenesis, which could be associated to some pathological processes such as oxidative stress, endoplasmic reticulum (ER) stress, impaired protein degradation, and mitochondrial dysfunction...
September 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27635664/an-11-mer-amyloid-beta-peptide-fragment-provokes-chemical-mutations-and-parkinsonian-biomarker-aggregation-in-dopaminergic-cells-a-novel-road-map-for-transfected-parkinson-s
#19
Parijat Kabiraj, Jose Eduardo Marin, Armando Varela-Ramirez, Mahesh Narayan
Amyloid beta (Aβ) aggregation is generally associated with Alzheimer's onset. Here, we demonstrate that incubation of dopaminergic SH-SY5Y cells with an Aβ peptide fragment (an 11-mer composed of residues 25-35; Aβ (25-35)) results in elevated intracellular nitrosative stress and induces chemical mutation of protein disulfide isomerase (PDI), an endoplasmic reticulum-resident oxidoreductase chaperone. Furthermore, Aβ (25-35) provokes aggregation of both the minor and major biomarkers of Parkinson's disease, namely, synphilin-1 and α-synuclein, respectively...
November 16, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27616576/bibenzyl-compound-20c-protects-against-endoplasmic-reticulum-stress-in-tunicamycin-treated-pc12-cells-in-vitro
#20
Zheng Mou, Yu-He Yuan, Yu-Xia Lou, Yang Heng, Ju-Yang Huang, Cong-Yuan Xia, Yan Gao, Cheng-Gen Zhu, Shi-Feng Chu, Piao Luo, Jian-Gong Shi, Nai-Hong Chen
AIM: Accumulation of α-synuclein (α-syn) in the brain is a characteristic of Parkinson's disease (PD). In this study, we investigated whether treatment with tunicamycin, an endoplasmic reticulum (ER) stress inducer, led to the accumulation of α-syn in PC12 cells, and where α-syn protein was accumulated, and finally, whether bibenzyl compound 20c, a novel compound isolated from Gastrodia elata (Tian ma), could alleviate the accumulation of α-syn and ER stress activation in tunicamycin-treated PC12 cells...
December 2016: Acta Pharmacologica Sinica
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