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N acetyl cysteine and parkinson

Esteban Luna, Samantha C Decker, Dawn M Riddle, Anna Caputo, Bin Zhang, Tracy Cole, Carrie Caswell, Sharon X Xie, Virginia M Y Lee, Kelvin C Luk
The accumulation of misfolded α-synuclein (aSyn) and neuron loss define several neurodegenerative disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the precise relationship between pathology and neurotoxicity and why these processes disproportionately affect certain neuron subpopulations are poorly understood. We show here that Math2-expressing neurons in the hippocampal Cornu ammonis (CA), a region significantly affected by aSyn pathology in advanced PD and DLB, are highly susceptible to pathological seeding with pre-formed fibrils (PFFs), in contrast to dentate gyrus neurons, which are relatively spared...
June 2018: Acta Neuropathologica
Xiao Xu Bai, Li Gu, Hui Min Yang, Shao Song Xi, Ning Xia, Song Zhang, Hong Zhang
Clinical epidemiological studies have shown that there is a link between Parkinson's disease (PD) and cancer, but how PD regulates cancer development remains unknown. In our study, the effect of metabotropic glutamate receptor 5 (mGlu5 ) on hepatoma was explored in a rotenone-induced PD model both in vitro and in vivo. We found that conditioned media derived from MN9D dopaminergic neuronal cells by rotenone-induced toxicity inhibited the growth, migration, invasion and promoted apoptosis of Hepa1-6 cells, which corresponded with decreased expression of mGlu5 ...
May 15, 2018: Toxicology Letters
Weelic Chong, Jessica Jiménez, Matthew McIIvin, Mak A Saito, Gunnar F Kwakye
This study examined the role of alpha-synuclein in regulating cadmium (Cd)-induced neurotoxicity using the N27 dopaminergic neuronal model of Parkinson's disease (PD) that stably expresses wild-type human α-synuclein (α-Syn) or empty vector (Vec) control. We report that α-Syn significantly increased Cd-induced cytotoxicity as compared to Vec control cells upon 24 h exposure. To explore the cellular mechanisms, we examined oxidative stress, caspase activation, and Cd uptake and intracellular accumulation...
March 28, 2017: Neurotoxicity Research
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
Hongjun Xie, Jie Wu
Silica nanoparticles (SiO2-NPs) are widely applied in diagnosis, imaging, and drug delivery of central nervous diseases. Previously, we found that SiO2-NPs enter the brain and, more specifically, the dopaminergic neurons in the striatum. Whether SiO2-NPs have neurotoxicity and contribute to development of Parkinson's disease (PD) remains unclear. In this study, we investigated the effect of SiO2-NPs on PC12 cells, a dopaminergic neuron-like cell line. We showed that SiO2-NPs up-regulated α-synuclein expression, and N-acetyl cysteine reduced α-synuclein...
October 25, 2016: Chemico-biological Interactions
Yuetao Zhou, Xiaolong Shi, Hong Chen, Shaqiu Zhang, Madhuri S Salker, Andreas F Mack, Michael Föller, Tak W Mak, Yogesh Singh, Florian Lang
DJ-1/Park7 is a redox-sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ-1 gene deletion exacerbates the progression of Parkinson's disease presumably by augmenting oxidative stress. Formation of reactive oxygen species (ROS) is paralleled by activation of the Na(+) /H(+) exchanger 1 (NHE1). ROS formation in CD4(+) T cells plays a decisive role in regulating inflammatory responses. In the present study, we explored whether DJ-1 is expressed in CD4(+) T cells, and affects ROS production as well as NHE1 in those cells...
November 2017: Journal of Cellular Physiology
Daniel A Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A Wintering, Jingli Cai, Xiatao Wei, Anthony J Bazzan, Li Zhong, Brendan Bowen, Charles M Intenzo, Lorraine Iacovitti, Andrew B Newberg
BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson's disease (PD). METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD...
2016: PloS One
Simone Olgiati, Matej Skorvanek, Marialuisa Quadri, Michelle Minneboo, Josja Graafland, Guido J Breedveld, Ramon Bonte, Zeliha Ozgur, Mirjam C G N van den Hout, Kees Schoonderwoerd, Frans W Verheijen, Wilfred F J van IJcken, Hsin Fen Chien, Egberto Reis Barbosa, Hsiu-Chen Chang, Szu-Chia Lai, Tu-Hsueh Yeh, Chin-Song Lu, Yah-Huei Wu-Chou, Anneke J A Kievit, Vladimir Han, Zuzana Gdovinova, Robert Jech, Robert M W Hofstra, George J G Ruijter, Wim Mandemakers, Vincenzo Bonifati
BACKGROUND: ECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fatty acids. Recently, ECHS1 mutations were shown to cause a new severe metabolic disorder presenting as Leigh or Leigh-like syndromes. The objective of this study was to describe a family with 2 siblings affected by different dystonic disorders as a resulting phenotype of ECHS1 mutations. METHODS: Clinical evaluation, MRI imaging, genome-wide linkage, exome sequencing, urine metabolite profiling, and protein expression studies were performed...
July 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Maurizio Remelli, Massimiliano Peana, Serenella Medici, Malgorzata Ostrowska, Elzbieta Gumienna-Kontecka, Maria Antonietta Zoroddu
A protected 30-amino acid fragment, Acetyl-SPDEKHELMIQLQKLDYTVGFCGDGANDCG-Amide, Acetyl-Ser-Pro-Asp-Glu-Lys-His-Glu-Leu-Met-Ile-Gln-Leu-Gln-Lys-Leu-Asp-Tyr-Thr-Val-Gly-Phe-Cys-Gly-Asp-Gly-Ala-Asn-Asp-Cys-Gly-Amide, encompassing the sequence from residues 1164 to 1193 in the encoded protein from Parkinson's disease gene Park9 (YPk9), was studied for manganese and zinc binding. Manganese exposure is considered to be an environmental risk factor connected to PD and PD-like syndrome. Research into the genetic and environmental risk factors involved in disease susceptibility has recently uncovered a link existing between Park9 and manganese...
March 28, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Negin Nouraei, Lauren Zarger, Justin N Weilnau, Jimin Han, Daniel M Mason, Rehana K Leak
The glutathione precursor N-acetyl-L-cysteine (NAC) is currently being tested on Parkinson's patients for its neuroprotective properties. Our studies have shown that NAC can elicit protection in glutathione-independent manners in vitro. Thus, the goal of the present study was to establish an animal model of NAC-mediated protection in which to dissect the underlying mechanism. Mice were infused intrastriatally with the oxidative neurotoxicant 6-hydroxydopamine (6-OHDA; 4 μg) and administered NAC intraperitoneally (100mg/kg)...
April 1, 2016: Toxicology and Applied Pharmacology
Reno C Reyes, Giordano Fabricio Cittolin-Santos, Ji-Eun Kim, Seok Joon Won, Angela M Brennan-Minnella, Maya Katz, Graham A Glass, Raymond A Swanson
N-acetyl cysteine (NAC) supports the synthesis of glutathione (GSH), an essential substrate for fast, enzymatically catalyzed oxidant scavenging and protein repair processes. NAC is entering clinical trials for adrenoleukodystrophy, Parkinson's disease, schizophrenia, and other disorders in which oxidative stress may contribute to disease progression. However, these trials are hampered by uncertainty about the dose of NAC required to achieve biological effects in human brain. Here we describe an approach to this issue in which mice are used to establish the levels of NAC in cerebrospinal fluid (CSF) required to affect brain neurons...
January 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Takujiro Homma, Junichi Fujii
Glutathione (GSH), an abundant tripeptidyl molecule, plays pivotal roles in protecting cells against oxidative stress-induced cellular damage and in detoxifying xenobiotics and drug metabolism. GSH is now entering a new era of therapeutic applications. Decreased GSH levels are associated with the common features of aging as well as of a wide range of pathological conditions, including neurodegenerative disorders. Notably, GSH depletion and/or alterations in its metabolism appear to be crucial in the onset of Parkinson's disease...
2015: Current Drug Metabolism
Ning Xia, Qian Zhang, Shu Ting Wang, Li Gu, Hui Min Yang, Li Liu, Rachit Bakshi, Hui Yang, Hong Zhang
Glutamate excitotoxicity contributes to the development of Parkinson's disease (PD) and pharmacological blockade of metabotropic glutamate receptor 5 (mGluR5) has beneficial anti-akinetic effects in animal models of PD; however, the mechanism by which these antagonists alleviate PD symptoms is largely unknown. In our study, the effects of mGluR5 inhibition on DNA damage were investigated in a rotenone-induced model of PD. We first found that the selective mGluR5 antagonist, 2-methyl-6- (phenylethynyl) pyridine, prevented rotenone-induced DNA damage in MN9D dopaminergic neurons through a mechanism involving the downregulation of intracellular calcium release which was associated with a reduction in endoplasmic reticulum stress and reactive oxygen species (ROS)-related mitochondrial dysfunction...
December 2015: Free Radical Biology & Medicine
Barbara Benassi, Giuseppe Filomeni, Costanza Montagna, Caterina Merla, Vanni Lopresto, Rosanna Pinto, Carmela Marino, Claudia Consales
Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss, with an etiopathogenesis involving both genetic and environmental factors. The occupational/residential exposure to the electromagnetic fields has been recently associated with an increased risk of neurodegenerative diseases; it has been thus proposed that the extremely low frequency magnetic field (ELF-MF) may contribute to neurodegenerative etiopathogenesis, as its interaction with biological systems directly impairs redox homeostasis in specific areas of the brain...
August 2016: Molecular Neurobiology
Goutam Kumar Tanti, Shweta Pandey, Shyamal K Goswami
SG2NA in association with striatin and zinedin forms a striatin family of WD-40 repeat proteins. This family of proteins functions as scaffold in different signal transduction pathways. They also act as a regulatory subunit of protein phosphatase 2A. We have shown that SG2NA which evolved first in the metazoan evolution among the striatin family members expresses different isoforms generated out of alternative splicing. We have also shown that SG2NA protects cells from oxidative stress by recruiting DJ-1 and Akt to mitochondria and membrane in the post-mitotic neuronal cells...
August 7, 2015: Biochemical and Biophysical Research Communications
Paresh Prajapati, Lakshmi Sripada, Kritarth Singh, Khyati Bhatelia, Rochika Singh, Rajesh Singh
Parkinson's disease (PD) is a complex neurological disorder of the elderly population and majorly shows the selective loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) region of the brain. The mechanisms leading to increased cell death of DAergic neurons are not well understood. Tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine is elevated in blood, CSF and striatum region of the brain in PD patients. The increased level of TNF-α and its role in pathogenesis of PD are not well understood...
March 2015: Biochimica et Biophysica Acta
Victor S Van Laar, Nikita Roy, Annie Liu, Swati Rajprohat, Beth Arnold, April A Dukes, Cory D Holbein, Sarah B Berman
Disruption of the dynamic properties of mitochondria (fission, fusion, transport, degradation, and biogenesis) has been implicated in the pathogenesis of neurodegenerative disorders, including Parkinson's disease (PD). Parkin, the product of gene PARK2 whose mutation causes familial PD, has been linked to mitochondrial quality control via its role in regulating mitochondrial dynamics, including mitochondrial degradation via mitophagy. Models using mitochondrial stressors in numerous cell types have elucidated a PINK1-dependent pathway whereby Parkin accumulates on damaged mitochondria and targets them for mitophagy...
February 2015: Neurobiology of Disease
Sarah W Yip, Marc N Potenza
Preclinical and clinical research implicate several neurotransmitter systems in the pathophysiology of gambling disorder (GD). In particular, neurobiological research suggests alterations in serotonergic, dopaminergic, glutamatergic and opioidergic functioning. The relative efficacy of medications targeting these systems remains a topic of ongoing research, and there is currently no Food and Drug Administration (FDA) approved medication with an indication for GD. Considering co-occurring disorders may be particularly important when devising a treatment plan for GD: extant data suggest that the opioid antagonist naltrexone may by the most effective form of current pharmacotherapy for GD, particularly for individuals with a co-occurring substance-use disorder (SUD) or with a family history of alcoholism...
June 1, 2014: Current Treatment Options in Psychiatry
Xi Lu, Jeong Sook Kim-Han, Steve Harmon, Shelly E Sakiyama-Elbert, Karen L O'Malley
6-hydroxydopamine (6-OHDA) is one of the most commonly used toxins for modeling degeneration of dopaminergic (DA) neurons in Parkinson's disease. 6-OHDA also causes axonal degeneration, a process that appears to precede the death of DA neurons. To understand the processes involved in 6-OHDA-mediated axonal degeneration, a microdevice designed to isolate axons fluidically from cell bodies was used in conjunction with green fluorescent protein (GFP)-labeled DA neurons. Results showed that 6-OHDA quickly induced mitochondrial transport dysfunction in both DA and non-DA axons...
2014: Molecular Neurodegeneration
F I Tarazi, Z T Sahli, M Wolny, S A Mousa
The prevalence of Parkinson's disease (PD) increases with age and is projected to increase in parallel to the rising average age of the population. The disease can have significant health-related, social, and financial implications not only for the patient and the caregiver, but for the health care system as well. While the neuropathology of this neurodegenerative disorder is fairly well understood, its etiology remains a mystery, making it difficult to target therapy. The currently available drugs for treatment provide only symptomatic relief and do not control or prevent disease progression, and as a result patient compliance and satisfaction are low...
November 2014: Pharmacology & Therapeutics
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