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parkinson's disease and mitochondria

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https://www.readbyqxmd.com/read/28917260/roles-of-sigma-1-receptors-on-mitochondrial-functions-relevant-to-neurodegenerative-diseases
#1
REVIEW
Tzu-Yu Weng, Shang-Yi Anne Tsai, Tsung-Ping Su
The sigma-1 receptor (Sig-1R) is a chaperone that resides mainly at the mitochondrion-associated endoplasmic reticulum (ER) membrane (called the MAMs) and acts as a dynamic pluripotent modulator in living systems. At the MAM, the Sig-1R is known to play a role in regulating the Ca(2+) signaling between ER and mitochondria and in maintaining the structural integrity of the MAM. The MAM serves as bridges between ER and mitochondria regulating multiple functions such as Ca(2+) transfer, energy exchange, lipid synthesis and transports, and protein folding that are pivotal to cell survival and defense...
September 16, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28916538/analysis-of-blood-based-gene-expression-in-idiopathic-parkinson-disease
#2
Ron Shamir, Christine Klein, David Amar, Eva-Juliane Vollstedt, Michael Bonin, Marija Usenovic, Yvette C Wong, Ales Maver, Sven Poths, Hershel Safer, Jean-Christophe Corvol, Suzanne Lesage, Ofer Lavi, Günther Deuschl, Gregor Kuhlenbaeumer, Heike Pawlack, Igor Ulitsky, Meike Kasten, Olaf Riess, Alexis Brice, Borut Peterlin, Dimitri Krainc
OBJECTIVE: To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). METHODS: Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature...
September 15, 2017: Neurology
https://www.readbyqxmd.com/read/28880525/mitoneet-cisd1-knockout-mice-show-signs-of-striatal-mitochondrial-dysfunction-and-a-parkinson-s-disease-phenotype
#3
Werner J Geldenhuys, Stanley A Benkovic, Li Lin, Heather M Yonutas, Samuel D Crish, Patrick G Sullivan, Altaf S Darvesh, Candice M Brown, Jason Richardson
Mitochondrial dysfunction is thought to play a significant role in neurodegeneration observed in Parkinson's disease (PD), yet the mechanisms underlying this pathology remain unclear. Here, we demonstrate that loss of mitoNEET (CISD1), an iron-sulfur containing protein which regulates mitochondrial bioenergetics, results in mitochondrial dysfunction and loss of striatal dopamine and tyrosine hydroxylase. Mitochondria isolated from mice lacking mitoNEET were dysfunctional as revealed by elevated reactive oxygen species (ROS) and reduced capacity to produce ATP...
September 7, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28874699/metal-concentrations-and-distributions-in-the-human-olfactory-bulb-in-parkinson-s-disease
#4
Bronwen Gardner, Birger V Dieriks, Steve Cameron, Lakshini H S Mendis, Clinton Turner, Richard L M Faull, Maurice A Curtis
In Parkinson's disease (PD), the olfactory bulb is typically the first region in the body to accumulate alpha-synuclein aggregates. This pathology is linked to decreased olfactory ability, which becomes apparent before any motor symptoms occur, and may be due to a local metal imbalance. Metal concentrations were investigated in post-mortem olfactory bulbs and tracts from 17 human subjects. Iron (p < 0.05) and sodium (p < 0.01) concentrations were elevated in the PD olfactory bulb. Combining laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry, iron and copper were evident at very low levels in regions of alpha-synuclein aggregation...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28865316/oxidative-species-induced-excitonic-transport-in-tubulin-aromatic-networks-potential-implications-for-neurodegenerative-disease
#5
P Kurian, T O Obisesan, T J A Craddock
Oxidative stress is a pathological hallmark of neurodegenerative tauopathic disorders such as Alzheimer's disease and Parkinson's disease-related dementia, which are characterized by altered forms of the microtubule-associated protein (MAP) tau. MAP tau is a key protein in stabilizing the microtubule architecture that regulates neuron morphology and synaptic strength. When MAP tau is degraded in tauopathic disorders, neuron dysfunction results. The precise role of reactive oxygen species (ROS) in the tauopathic disease process, however, is poorly understood...
August 24, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28852477/endoplasmic-reticulum-mitochondria-tethering-in-neurodegenerative-diseases
#6
REVIEW
Yi Liu, Xiongwei Zhu
Endoplasmic reticulum (ER) and mitochondria are tubular organelles with a characteristic "network structure" that facilitates the formation of inter-organellar connections. As a result, mitochondria-associated ER membranes (MAMs), a subdomain of the ER that is tightly linked to and communicates with mitochondria, serve multiple physiological functions including lipid synthesis and exchange, calcium signaling, bioenergetics, and apoptosis. Importantly, emerging evidence suggests that the abnormality and dysfunction of MAMs have been involved in various neurodegenerative disorders including Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28844784/dieldrin-induced-neurotoxicity-involves-impaired-mitochondrial-bioenergetics-and-an-endoplasmic-reticulum-stress-response-in-rat-dopaminergic-cells
#7
Jordan T Schmidt, Anna Rushin, Jonna Boyda, Christopher Laurence Souders, Christopher J Martyniuk
Mitochondria are sensitive targets of environmental chemicals. Dieldrin (DLD) is an organochlorine pesticide that remains a human health concern due to high lipid bioaccumulation, and it has been epidemiologically associated to an increased risk for Parkinson's disease (PD). As mitochondrial dysfunction is involved in the etiology of PD, this study aimed to determine whether DLD impaired mitochondrial bioenergetics in dopaminergic cells. Rat immortalized dopaminergic N27 cells were treated for 24 or 48h with one dose of either a solvent control, 2...
August 24, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28842646/a-missense-mt-nd5-mutation-in-differentiated-parkinson-disease-cytoplasmic-hybrid-induces-ros-dependent-dna-damage-response-amplified-by-drosha
#8
Daniela Pignataro, Sofia Francia, Francesca Zanetta, Giulia Brenna, Stefania Brandini, Anna Olivieri, Antonio Torroni, Giuseppe Biamonti, Alessandra Montecucco
Genome integrity is continuously threatened by endogenous sources of DNA damage including reactive oxygen species (ROS) produced by cell metabolism. Factors of the RNA interference (RNAi) machinery have been recently involved in the cellular response to DNA damage (DDR) in proliferating cells. To investigate the impact of component of RNAi machinery on DDR activation in terminally differentiated cells, we exploited cytoplasmic hybrid (cybrid) cell lines in which mitochondria of sporadic Parkinson's disease patients repopulate neuroblastoma SH-SY5Y-Rho(0) cells...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28840449/from-mitochondrial-function-to-neuroprotection-an-emerging-role-for-methylene-blue
#9
REVIEW
Donovan Tucker, Yujiao Lu, Quanguang Zhang
Methylene blue (MB) is a well-established drug with a long history of use, owing to its diverse range of use and its minimal side effect profile. MB has been used classically for the treatment of malaria, methemoglobinemia, and carbon monoxide poisoning, as well as a histological dye. Its role in the mitochondria, however, has elicited much of its renewed interest in recent years. MB can reroute electrons in the mitochondrial electron transfer chain directly from NADH to cytochrome c, increasing the activity of complex IV and effectively promoting mitochondrial activity while mitigating oxidative stress...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28838811/mitochondrial-calcium-imbalance-in-parkinson-s-disease
#10
REVIEW
Marthe H R Ludtmann, Andrey Y Abramov
Multiple factors are involved in the mechanism(s) of neuronal loss in neurodegenerative disorders whilst mitochondria are thought to play a central role in neurodegeneration of Parkinson's disease. Mitochondria are vital to cellular functions by supplying energy in form of ATP and affect cell physiology via calcium, ROS and signalling proteins. Changes in mitochondrial calcium homeostasis and ROS overproduction can induce cell death by triggering mitochondrial permeability transition pore opening. One of the major triggers for PTP is mitochondrial calcium overload...
August 26, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28827552/baicalein-prevents-6-ohda-ascorbic-acid-induced-calcium-dependent-dopaminergic-neuronal-cell-death
#11
Sheng-Fang Wang, Liang-Feng Liu, Ming-Yue Wu, Cui-Zan Cai, Huanxing Su, Jieqiong Tan, Jia-Hong Lu, Min Li
6-OHDA plus ascorbic acid (AA) has long been used to induce Parkinson's disease in rodents, while only 6-OHDA is commonly used to induce cell damage in cellular PD models. AA was believed to act as an anti-oxidant to prevent the degradation of 6-OHDA; however, some studies suggested that AA dramatically enhanced the selectivity and toxicity of 6-OHDA. To understand the mechanisms by which 6-OHDA/AA induces cell death, we established a 6-OHDA/AA cell toxicity model in human dopaminergic neuroblastoma SH-SY5Y cells...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28822073/isorhynchophylline-attenuates-mpp-induced-apoptosis-through-endoplasmic-reticulum-stress-and-mitochondria-dependent-pathways-in-pc12-cells-involvement-of-antioxidant-activity
#12
Xiao-Ming Li, Xiao-Jie Zhang, Miao-Xian Dong
Endoplasmic reticulum stress (ERS) and mitochondrial dysfunctions are thought to be involved in the dopaminergic neuronal death in Parkinson's disease (PD). In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP(+)-induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP(+)-triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway...
August 18, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28815529/mitochondrial-associated-membranes-in-parkinson-s-disease
#13
Nobutaka Hattori, Taku Arano, Taku Hatano, Akio Mori, Yuzuru Imai
Parkinson's disease (PD) is a common neurodegenerative disorder, with ageing being a major risk factor. Accordingly, estimates predict an increasing number of PD patients due to our expanding life span. Consequently, developing a true disease-modifying therapy is necessary. In this regard, monogenic PD offers a suitable means for determining pathogenesis. Among monogenic forms of PD, mitochondrial dysfunction may be a major cause and is also likely to be involved in sporadic PD. Thus, mitochondrial impairment may be a common pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28806519/pluronic-p85-f68-micelles-of-baicalein-could-interfere-with-mitochondria-to-overcome-mrp2-mediated-efflux-and-offer-improved-anti-parkinsonian-activity
#14
Tongkai Chen, Ye Li, Chuwen Li, Xiang Yi, Ruibing Wang, Simon Ming-Yuen Lee, Ying Zheng
Overexpression of the drug efflux transporter multidrug resistance-associated protein 2 (MRP2) in the gastrointestinal tract and blood-brain barrier compromises the oral delivery of drugs to the circulation system and brain in the treatment of Parkinson's disease (PD). In this study, we aim to develop small-sized Pluronic P85/F68 micelles loaded with baicalein (B-MCs) to overcome MRP2-mediated efflux and to investigate related mechanism, as well as the anti-Parkinsonian efficacy. Spherical and sustained-release B-MCs have a mean particle size of 40...
August 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28800639/mitochondrial-impairment-and-melatonin-protection-in-parkinsonian-mice-do-not-depend-of-inducible-or-neuronal-nitric-oxide-synthases
#15
Ana López, Francisco Ortiz, Carolina Doerrier, Carmen Venegas, Marisol Fernández-Ortiz, Paula Aranda, María E Díaz-Casado, Beatriz Fernández-Gil, Eliana Barriocanal-Casado, Germaine Escames, Luis C López, Darío Acuña-Castroviejo
MPTP-mouse model constitutes a well-known model of neuroinflammation and mitochondrial failure occurring in Parkinson's disease (PD). Although it has been extensively reported that nitric oxide (NO●) plays a key role in the pathogenesis of PD, the relative roles of nitric oxide synthase isoforms iNOS and nNOS in the nigrostriatal pathway remains, however, unclear. Here, the participation of iNOS/nNOS isoforms in the mitochondrial dysfunction was analyzed in iNOS and nNOS deficient mice. Our results showed that MPTP increased iNOS activity in substantia nigra and striatum, whereas it sharply reduced complex I activity and mitochondrial bioenergetics in all strains...
2017: PloS One
https://www.readbyqxmd.com/read/28798236/the-unintended-mitochondrial-uncoupling-effects-of-the-fda-approved-anti-helminth-drug-nitazoxanide-mitigates-experimental-parkinsonism-in-mice
#16
Niharika Amireddy, Srinivas N Puttapaka, Ravali L Vinnakota, Halley G Ravuri, Swaroop Thonda, Shasi V Kalivendi
Mitochondria plays a primary role in the pathophysiology of Parkinson's disease (PD) and small molecules that counteract the initial stages of disease may offer therapeutic benefit. In this regard, we have examined whether the off-target effects of the FDA approved anti-helminth drug, nitazoxanide (NTZ) on mitochondrial respiration could possess any therapeutic potential for PD. Results indicate that MPP(+) induced loss in oxygen consumption rate (OCR) and ATP production by mitochondria were ameliorated by NTZ in real-time by virtue of its mild-uncoupling effect...
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28797885/mitophagy-in-neurodegenerative-diseases
#17
REVIEW
Carlo Rodolfo, Silvia Campello, Francesco Cecconi
Neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), are a complex "family" of pathologies, characterised by the progressive loss of neurons and/or neuronal functions, leading to severe physical and cognitive inabilities in affected patients. These syndromes, despite differences in the causative events, the onset, and the progression of the disease, share as common features the presence of aggregate-prone neuro-toxic proteins, in the form of aggresomes and/or inclusion bodies, perturbing cellular homeostasis and neuronal function (Popovic et al...
August 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28791420/melatonin-as-a-mitochondrial-protector-in-neurodegenerative-diseases
#18
REVIEW
Pawaris Wongprayoon, Piyarat Govitrapong
Mitochondria are crucial organelles as their role in cellular energy production of eukaryotes. Because the brain cells demand high energy for maintaining their normal activities, disturbances in mitochondrial physiology may lead to neuropathological events underlying neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Melatonin is an endogenous compound with a variety of physiological roles. In addition, it possesses potent antioxidant properties which effectively play protective roles in several pathological conditions...
August 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28790012/mdivi-1-ameliorates-early-brain-injury-after-subarachnoid-hemorrhage-via-the-suppression-of-inflammation-related-blood-brain-barrier-disruption-and-endoplasmic-reticulum-stress-based-apoptosis
#19
Lin-Feng Fan, Ping-You He, Yu-Cong Peng, Qing-Hua Du, Yi-Jun Ma, Jian-Xiang Jin, Hang-Zhe Xu, Jian-Ru Li, Zhi-Jiang Wang, Sheng-Long Cao, Tao Li, Feng Yan, Chi Gu, Lin Wang, Gao Chen
Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms...
August 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28782874/in-vivo-imaging-reveals-mitophagy-independence-in-the-maintenance-of-axonal-mitochondria-during-normal-aging
#20
Xu Cao, Haiqiong Wang, Zhao Wang, Qingyao Wang, Shuang Zhang, Yuanping Deng, Yanshan Fang
Mitophagy is thought to be a critical mitochondrial quality control mechanism in neurons and has been extensively studied in neurological disorders such as Parkinson's disease. However, little is known about how mitochondria are maintained in the lengthy neuronal axons in the context of physiological aging. Here, we utilized the unique Drosophila wing nerve model and in vivo imaging to rigorously profile changes in axonal mitochondria during aging. We revealed that mitochondria became fragmented and accumulated in aged axons...
October 2017: Aging Cell
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