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https://www.readbyqxmd.com/read/27913844/global-dna-methylation-profiling-of-manganese-exposed-human-neuroblastoma-sh-sy5y-cells-reveals-epigenetic-alterations-in-parkinson-s-disease-associated-genes
#1
Prashant Tarale, Saravanadevi Sivanesan, Atul P Daiwile, Reinhard Stöger, Amit Bafana, Pravin K Naoghare, Devendra Parmar, Tapan Chakrabarti, Krishnamurthi Kannan
Manganese (Mn) is an essential trace element required for optimal functioning of cellular biochemical pathways in the central nervous system. Elevated exposure to Mn through environmental and occupational exposure can cause neurotoxic effects resulting in manganism, a condition with clinical symptoms identical to idiopathic Parkinson's disease. Epigenetics is now recognized as a biological mechanism involved in the etiology of various diseases. Here, we investigated the role of DNA methylation alterations induced by chronic Mn (100 µM) exposure in human neuroblastoma (SH-SY5Y) cells in relevance to Parkinson's disease...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27911343/pink1-parkin-and-mitochondrial-quality-control-what-can-we-learn-about-parkinson-s-disease-pathobiology
#2
Dominika Truban, Xu Hou, Thomas R Caulfield, Fabienne C Fiesel, Wolfdieter Springer
The first clinical description of Parkinson's disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process known as mitophagy...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27908782/adaptive-responses-of-neuronal-mitochondria-to-bioenergetic-challenges-roles-in-neuroplasticity-and-disease-resistance
#3
REVIEW
Sophia M Raefsky, Mark P Mattson
An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27906179/pink1-dependent-phosphorylation-of-pink1-and-parkin-is-essential-for-mitochondrial-quality-control
#4
Na Zhuang, Lin Li, She Chen, Tao Wang
Mitochondrial dysfunction has been linked to the pathogenesis of a large number of inherited diseases in humans, including Parkinson's disease, the second most common neurodegenerative disorder. The Parkinson's disease genes pink1 and parkin, which encode a mitochondrially targeted protein kinase, and an E3 ubiquitin ligase, respectively, participate in a key mitochondrial quality-control pathway that eliminates damaged mitochondria. In the current study, we established an in vivo PINK1/Parkin-induced photoreceptor neuron degeneration model in Drosophila with the aim of dissecting the PINK1/Parkin pathway in detail...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27905618/mechanism-of-%C3%AE-synuclein-translocation-through-a-vdac-nanopore-revealed-by-energy-landscape-modeling-of-escape-time-distributions
#5
David P Hoogerheide, Philip A Gurnev, Tatiana K Rostovtseva, Sergey M Bezrukov
We probe the energy landscape governing the passage of α-synuclein, a natural "diblock copolymer"-like polypeptide, through a nanoscale pore. α-Synuclein is an intrinsically disordered neuronal protein associated with Parkinson's pathology. The motion of this electrically heterogeneous polymer in the β-barrel voltage-dependent anion channel (VDAC) of the mitochondrial outer membrane strongly depends on the properties of both the charged and uncharged regions of the α-synuclein polymer. We model this motion in two ways...
December 1, 2016: Nanoscale
https://www.readbyqxmd.com/read/27895381/reactive-oxygen-species-induce-neurite-degeneration-before-induction-of-cell-death
#6
Koji Fukui
Reactive oxygen species (ROS) induce neuronal cell death in a time- and concentration-dependent manner. Treatment of cultured cells with a low concentration of hydrogen peroxide induces neurite degeneration, but not cell death. Neurites (axons and dendrites) are vulnerable to ROS. Neurite degeneration (shrinkage, accumulation, and fragmentation) has been found in neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, the mechanism of ROS-related neurite degeneration is not fully understood...
November 2016: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/27894919/resveratrol-attenuates-mpp-induced-mitochondrial-dysfunction-and-cell-apoptosis-via-akt-gsk-3%C3%AE-pathway-in-sn4741-cells
#7
Weijun Zeng, Wei Zhang, Fangfang Lu, Li Gao, Guodong Gao
Oxidative stress and mitochondrial dysfunction play crucial role in the dopaminergic neurons death, which is the pathological feature of Parkinson's disease (PD). Resveratrol (Res), a polyphenol derived from grapes and blueberries, has been reported to reduce oxidative stress injury and to restore mitochondrial function. In this study, we aimed to explore the underlying molecular mechanism of the beneficial effects of Res against MPP+- induced mitochondrial dysfunction and cell apoptosis in SN4741 cells. The data showed that Res significantly alleviated MPP+- induce cytotoxicity and restored MPP+- induced mitochondrial dysfunction in SN4741 cells...
November 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27884192/role-of-cytochrome-c-in-%C3%AE-synuclein-radical-formation-implications-of-%C3%AE-synuclein-in-neuronal-death-in-maneb-and-paraquat-induced-model-of-parkinson-s-disease
#8
Ashutosh Kumar, Douglas Ganini, Ronald P Mason
BACKGROUND: The pathological features of Parkinson's disease (PD) include an abnormal accumulation of α-synuclein in the surviving dopaminergic neurons. Though PD is multifactorial, several epidemiological reports show an increased incidence of PD with co-exposure to pesticides such as Maneb and paraquat (MP). In pesticide-related PD, mitochondrial dysfunction and α-synuclein oligomers have been strongly implicated, but the link between the two has not yet been understood. Similarly, the biological effects of α-synuclein or its radical chemistry in PD is largely unknown...
November 24, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27882828/morinda-citrifolia-mitigates-rotenone-induced-striatal-neuronal-loss-in-male-sprague-dawley-rats-by-preventing-mitochondrial-pathway-of-intrinsic-apoptosis
#9
S Narasimhan Kishore Kumar, Jayakumar Deepthy, Uthamaraman Saraswathi, Mohan Thangarajeswari, Sathyamoorthy Yogesh Kanna, Pannerselvam Ezhil, Periandavan Kalaiselvi
OBJECTIVES: Parkinson disease (PD) is a neurodegenerative disorder affecting mainly the motor system, as a result of death of dopaminergic neurons in the substantia nigra pars compacta. The present scenario of research in PD is directed to identify novel molecules that can be administered individually or co-administered with L-Dopa to prevent the L-Dopa-Induced Dyskinesia (LID) like states that arise during chronic L-Dopa administration. Hence, in this study, we investigated whether Morinda citrifolia has therapeutic effects in rotenone-induced Parkinson's disease (PD) with special reference to mitochondrial dysfunction mediated intrinsic apoptosis...
November 24, 2016: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/27882077/potential-protective-effects-of-autophagy-activated-in-mpp-treated-astrocytes
#10
Cunzhou Shen, Wenbiao Xian, Hongyan Zhou, Ling Chen, Zhong Pei
Astrocytes, which have various important functions, have previously been associated with Parkinsons disease (PD), particularly in 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD. MPP+ is the toxic metabolite of MPTP and is generated by the enzymatic activity of monoamine oxidase B, which is predominantly located in astrocytes. MPP+ acts as a mitochondrial complex I inhibitor. Autophagy is an evolutionarily conserved self-digestion pathway in eukaryotic cells, which occurs in response to various types of stress, including starvation and oxidative stress...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27881168/loss-of-porin-function-in-dopaminergic-neurons-of-drosophila-is-suppressed-by-buffy
#11
P Githure M'Angale, Brian E Staveley
BACKGROUND: Mitochondrial porin, also known as the voltage-dependent anion channel (VDAC), is a multi-functional channel protein that shuttles metabolites between the mitochondria and the cytosol and implicated in cellular life and death decisions. The inhibition of porin under the control of neuronal Ddc-Gal4 result in short lifespan and in an age-dependent loss in locomotor function, phenotypes that are strongly associated with Drosophila models of Parkinson disease. METHODS: Loss of porin function was achieved through exploitation of RNA interference while derivative lines were generated by homologous recombination and tested by PCR...
November 24, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27879341/title-dynamin-functions-and-ligands-classical-mechanism-behind
#12
Mahaveer Singh, Hemant Jadhav, Tanya B
Dynamin is a GTPase, which plays a vital role in clathrin dependent endocytosis and other vesicular trafficking processes. Dynamin acts as scissor with debatable mechanism for newly formed vesicles originating from plasma membrane. Dynamin related proteins are important components in scission of various organelles such as clathrin coated vesicles, phagosomes and mitochondria, etc. helping in organelle division, viral resistance and mitochondrial fusion/division. Dysfunction and mutations in dynamin have been implicated in various disorders, where endocytic trafficking is involved, such as Alzheimer's, Parkinson's, Huntington's, Charcot-Marie Tooth disease, Heart failure, Schizophrenia, Epilepsy, Cancer, Optic atrophy, Down syndrome, Osteoporosis etc...
November 22, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27876560/subcutaneous-rotenone-rat-model-of-parkinson-s-disease-dose-exploration-study
#13
Zhen-Nian Zhang, Jing-Si Zhang, Jun Xiang, Zhong-Hai Yu, Wen Zhang, Min Cai, Xiang-Ting Li, Ting Wu, Wen-Wei Li, Ding-Fang Cai
Subcutaneous administration of rotenone has recently attracted attention because of its convenience, simplicity and efficacy in replicating features of Parkinson's disease (PD) in animal models. However, the wide range of doses reported in the literature makes it difficult to evaluate the effectiveness of this technique objectively. The aim of the present study was to identify the optimum dose of subcutaneous rotenone for establishing a model of PD. We injected male Wistar rats subcutaneously with one of three doses of rotenone (1...
November 19, 2016: Brain Research
https://www.readbyqxmd.com/read/27874000/defective-mitochondrial-dna-homeostasis-in-the-substantia-nigra-in-parkinson-disease
#14
Christian Dölle, Irene Flønes, Gonzalo S Nido, Hrvoje Miletic, Nelson Osuagwu, Stine Kristoffersen, Peer K Lilleng, Jan Petter Larsen, Ole-Bjørn Tysnes, Kristoffer Haugarvoll, Laurence A Bindoff, Charalampos Tzoulis
Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we study the complete spectrum of mtDNA changes, including deletions, copy-number variation and point mutations, in single neurons from the dopaminergic substantia nigra and other brain areas of individuals with Parkinson disease and neurologically healthy controls. We show that in dopaminergic substantia nigra neurons of healthy individuals, mtDNA copy number increases with age, maintaining the pool of wild-type mtDNA population in spite of accumulating deletions...
November 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27873462/mitochondrial-dysfunction-and-biogenesis-in-neurodegenerative-diseases-pathogenesis-and-treatment
#15
REVIEW
Mojtaba Golpich, Elham Amini, Zahurin Mohamed, Raymond Azman Ali, Norlinah Mohamed Ibrahim, Abolhassan Ahmadiani
Neurodegenerative diseases are a heterogeneous group of disorders that are incurable and characterized by the progressive degeneration of the function and structure of the central nervous system (CNS) for reasons that are not yet understood. Neurodegeneration is the umbrella term for the progressive death of nerve cells and loss of brain tissue. Because of their high energy requirements, neurons are especially vulnerable to injury and death from dysfunctional mitochondria. Widespread damage to mitochondria causes cells to die because they can no longer produce enough energy...
November 22, 2016: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27872751/novel-gene-tmem230-linked-to-parkinson-s-disease
#16
EDITORIAL
Diana A Olszewska, Conor Fearon, Tim Lynch
Mutations in six genes are known to cause Parkinson's disease (PD) (autosomal dominant: alpha-synuclein, LRRK2, VPS35 and autosomal recessive: Parkin, PINK1 and DJ1) and number of other genes are implicated. In a recent article Deng and colleagues studied a large four generation American family of European descent and linked mutations in a novel gene, transmembrane-protein 230 gene (TMEM230) with lewy body confirmed PD. The authors demonstrated that pathogenic TMEM230 variants in primary mouse neurons affected movement of synaptic vesicles suggesting that TMEM230 may slow vesicular transport...
2016: Journal of Clinical Movement Disorders
https://www.readbyqxmd.com/read/27867042/poly-adp-ribose-polymerase-1-hyperactivation-in-neurodegenerative-diseases-the-death-knell-tolls-for-neurons
#17
REVIEW
Parimala Narne, Vimal Pandey, Praveen Kumar Simhadri, Prakash Babu Phanithi
Neurodegeneration is a salient feature of chronic refractory brain disorders like Alzheimer's, Parkinson's, Huntington's, amyotropic lateral sclerosis and acute conditions like cerebral ischemia/reperfusion etc. The pathological protein aggregates, mitochondrial mutations or ischemic insults typifying these disease conditions collude with and intensify existing oxidative stress and attendant mitochondrial dysfunction. Interlocking these mechanisms is poly(ADP-ribose) polymerase (PARP-1) hyperactivation that invokes a distinct form of neuronal cell death viz...
November 17, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27866262/impairment-of-mitochondria-dynamics-by-human-a53t-%C3%AE-synuclein-and-rescue-by-nap-davunetide-in-a-cell-model-for-parkinson-s-disease
#18
T Q Melo, K C van Zomeren, M F R Ferrari, H W G M Boddeke, J C V M Copray
The formation of oligomers and aggregates of overexpressed or mutant α-synuclein play a role in the degeneration of dopaminergic neurons in Parkinson's disease by causing dysfunction of mitochondria, reflected in their disturbed mobility and production of ROS. The mode of action and mechanisms underlying this mitochondrial impairment is still unclear. We have induced stable expression of wild-type, A30P or A53T α-synuclein in neuronally differentiated SH-SY5Y neuroblastoma cells and studied anterograde and retrograde mitochondrial trafficking in this cell model for Parkinson's disease...
November 19, 2016: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/27859782/inhibition-of-the-mitochondrial-calcium-uniporter-mcu-rescues-dopaminergic-neurons-in-pink1-zebrafish
#19
Smijin Soman, Marcus Keatinge, Mahsa Moein, Marc DaCosta, Heather Mortiboys, Alexander Skupin, Sreedevi Sugunan, Michal Bazala, Jacek Kuznicki, Oliver Bandmann
Mutations in PTEN-induced putative kinase 1 (PINK1) are a cause of early onset Parkinson's disease (PD). Loss of PINK1 function causes dysregulation of mitochondrial calcium homeostasis, resulting in mitochondrial dysfunction and neuronal cell death. We report that both genetic and pharmacological inactivation of the mitochondrial calcium uniporter (MCU), located in the inner mitochondrial membrane, prevents dopaminergic neuronal cell loss in pink1(Y431) * mutant zebrafish (Danio rerio) via rescue of mitochondrial respiratory chain function...
November 12, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27848260/the-htra2-drosophila-model-of-parkinson-s-disease-is-suppressed-by-the-pro-survival-bcl-2-buffy
#20
P Githure M'Angale, Brian E Staveley
Mutations in High temperature requirement A2 (HtrA2), also designated PARK13, which lead to the loss of its protease activity, have been associated with Parkinson's disease (PD). HtrA2 is a mitochondrial protease that translocates to the cytosol upon the initiation of apoptosis where it participates in the abrogation of inhibitors of apoptosis (IAP) inhibition of caspases. Here, we demonstrate that the loss of the HtrA2 function in the dopaminergic neurons of Drosophila melanogaster results in PD-like phenotypes, and we attempt to restore the age-dependent loss in locomotor ability by co-expressing the sole pro-survival Bcl-2 homologue Buffy...
August 30, 2016: Genome Génome / Conseil National de Recherches Canada
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