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https://www.readbyqxmd.com/read/27736935/chemical-compensation-of-mitochondrial-phospholipid-depletion-in-yeast-and-animal-models-of-parkinson-s-disease
#1
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/27717874/temporary-removal-pharmaceutical-development-of-novel-lactate-based-6-fluoro-l-dopa-formulations
#2
Nunzio Denora, Angela Lopedota, Modesto De Candia, Saverio Cellamare, Leonardo Degennaro, Renzo Luisi, Antonietta Mele, Domenico Tricarico, Annalisa Cutrignelli, Valentino Laquintana, Cosimo D Altomare, Massimo Franco, Vincenzo Dimiccoli, Anna Tolomeo, Antonio Scilimati
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
October 4, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27556455/novel-redox-dependent-esterase-activity-ec-3-1-1-2-for-dj-1-implications-for-parkinson-s-disease
#3
Emmanuel Vázquez-Mayorga, Ángel G Díaz-Sánchez, Ruben K Dagda, Carlos A Domínguez-Solís, Raul Y Dagda, Cynthia K Coronado-Ramírez, Alejandro Martínez-Martínez
Mutations the in human DJ-1 (hDJ-1) gene are associated with early-onset autosomal recessive forms of Parkinson's disease (PD). hDJ-1/parkinsonism associated deglycase (PARK7) is a cytoprotective multi-functional protein that contains a conserved cysteine-protease domain. Given that cysteine-proteases can act on both amide and ester substrates, we surmised that hDJ-1 possessed cysteine-mediated esterase activity. To test this hypothesis, hDJ-1 was overexpressed, purified and tested for activity towards 4-nitrophenyl acetate (pNPA) as µmol of pNPA hydrolyzed/min/mg·protein (U/mg protein)...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27455809/-link-between-aluminum-neurotoxicity-and-neurodegenerative-disorders
#4
Masahiro Kawahara
Aluminum is an old element that has been known for a long time, but some of its properties are only now being discovered. Although environmentally abundant, aluminum is not essential for life; in fact, because of its specific chemical properties, aluminum inhibits more than 200 biologically important functions and exerts various adverse effects in plants, animals, and humans. Aluminum is a widely recognized neurotoxin. It has been suggested that there is a relationship between exposure to aluminum and neurodegenerative diseases, including dialysis encephalopathy, amyotrophic lateral sclerosis and parkinsonism dementia in the Kii Peninsula and Guam, as well as Alzheimer' s disease: however, this claim remains to be verified...
July 2016: Nihon Rinsho. Japanese Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27344208/neurodegeneration-in-tauopathies-and-synucleinopathies
#5
C Foguem, B Kamsu-Foguem
While increasing life expectancy is a major achievement, the global aging of societies raises a number of medical issues, such as the development of age-related disorders, including neurodegenerative diseases. The three main disease groups constituting the majority of neurodegenerative diseases are tauopathies, alpha-synucleinopathies and diseases due to repetitions of glutamine (including Huntington's disease). In each neurodegenerative disease, the accumulation of one or more aggregated proteins has been identified as the molecular signature of the disease (as seen, for example, in Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, amyotrophic lateral sclerosis and frontotemporal dementia)...
June 22, 2016: Revue Neurologique
https://www.readbyqxmd.com/read/27311820/melanin-and-neuromelanin-binding-of-drugs-and-chemicals-toxicological-implications
#6
REVIEW
Oskar Karlsson, Nils Gunnar Lindquist
Melanin is a polyanionic pigment that colors, e.g., the hair, skin and eyes. The pigment neuromelanin is closely related to melanin and is mainly produced in specific neurons of the substantia nigra. Certain drugs and chemicals bind to melanin/neuromelanin and are retained in pigment cells for long periods. This specific retention is thought to protect the cells but also to serve as a depot that slowly releases accumulated compounds and may cause toxicity in the eye and skin. Moreover, neuromelanin and compounds with high neuromelanin affinity have been suggested to be implicated in the development of adverse drug reactions in the central nervous system (CNS) as well as in the etiology of Parkinson's disease (PD)...
August 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27131990/discovery-of-3-aminopicolinamides-as-metabotropic-glutamate-receptor-subtype-4-mglu4-positive-allosteric-modulator-warheads-engendering-cns-exposure-and-in-vivo-efficacy
#7
Rocco D Gogliotti, Darren W Engers, Pedro M Garcia-Barrantes, Joseph D Panarese, Patrick R Gentry, Anna L Blobaum, Ryan D Morrison, J Scott Daniels, Analisa D Thompson, Carrie K Jones, P Jeffrey Conn, Colleen M Niswender, Craig W Lindsley, Corey R Hopkins
This letter describes the further chemical optimization of the picolinamide-derived family of mGlu4 PAMs wherein we identified a 3-amino substituent to the picolinamide warhead that engendered potency, CNS penetration and in vivo efficacy. From this optimization campaign, VU0477886 emerged as a potent (EC50=95nM, 89% Glu Max) mGlu4 PAM with an attractive DMPK profile (brain:plasma Kp=1.3), rat CLp=4.0mL/min/kg, t1/2=3.7h) and robust efficacy in our standard preclinical Parkinson's disease model, haloperidol-induced catalepsy (HIC)...
June 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/26896854/systematic-reviews-on-neurodevelopmental-and-neurodegenerative-disorders-linked-to-pesticide-exposure-methodological-features-and-impact-on-risk-assessment
#8
Antonio F Hernández, Beatriz González-Alzaga, Inmaculada López-Flores, Marina Lacasaña
BACKGROUND: Epidemiological data are not currently used in the risk assessment of chemical substances in a systematic and consistent manner. However, systematic reviews (SRs) could be useful for risk assessment as they appraise and synthesize the best epidemiological knowledge available. OBJECTIVES: To conduct a comprehensive literature search of SRs pertaining to pesticide exposure and various neurological outcomes, namely neurodevelopmental abnormalities, Parkinson's disease (PD) and Alzheimer's disease (AD), and to assess the potential contribution of SRs to the risk assessment process...
July 2016: Environment International
https://www.readbyqxmd.com/read/26885710/manganism-and-parkinson-s-disease-mn-ii-and-zn-ii-interaction-with-a-30-amino-acid-fragment
#9
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
https://www.readbyqxmd.com/read/26879225/microwave-fields-have-little-effect-on-%C3%AE-synuclein-aggregation-in-a-caenorhabditis-elegans-model-of-parkinson-s-disease
#10
David I de Pomerai, Nooria Iqbal, Ivan Lafayette, Archana Nagarajan, Mehri Kaviani Moghadam, April Fineberg, Tom Reader, Steve Greedy, Chris Smartt, David W P Thomas
Potential health effects of radiofrequency (RF) radiation from mobile phones arouse widespread public concern. RF fields from handheld devices near the brain might trigger or aggravate brain tumors or neurodegenerative diseases such as Parkinson's disease (PD). Aggregation of neural α-synuclein (S) is central to PD pathophysiology, and invertebrate models expressing human S have helped elucidate factors affecting the aggregation process. We have recently developed a transgenic strain of Caenorhabditis elegans carrying two S constructs: SC tagged with cyan (C) blue fluorescent protein (CFP), and SV with the Venus (V) variant of yellow fluorescent protein (YFP)...
February 2016: Bioelectromagnetics
https://www.readbyqxmd.com/read/26873872/coupling-of-the-non-amyloid-component-nac-domain-and-the-ktk-e-q-gv-repeats-stabilize-the-%C3%AE-synuclein-fibrils
#11
Liang Xu, Ruth Nussinov, Buyong Ma
The aggregates of α-synuclein (αS) are a major pathological hallmark of Parkinson's disease (PD) making their structure-function relationship important for rational drug design. Yet, the atomic structure of the αS aggregates is unavailable, making it difficult to understand the underlying aggregation mechanism. In this work, based on available experimental data, we examined plausible molecular structures of αS(20/30-110) fibrils for the first time by employing computational approaches. The optimized structure was used to investigate possible interactions with aggregation inhibitors...
October 4, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/26854325/environmental-and-occupational-risk-factors-for-progressive-supranuclear-palsy-case-control-study
#12
Irene Litvan, Peter S J Lees, Christopher R Cunningham, Shesh N Rai, Alexander C Cambon, David G Standaert, Connie Marras, Jorge Juncos, David Riley, Stephen Reich, Deborah Hall, Benzi Kluger, Yvette Bordelon, David R Shprecher
BACKGROUND: The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. METHODS: This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history...
May 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/26563795/neurotoxic-exposure-and-impairment-of-the-chemical-senses-of-taste-and-smell
#13
REVIEW
Richard L Doty
The chemical senses of taste and smell determine the flavor of foods and beverages, guide appropriate food intake, and warn of such environmental hazards as spoiled or poisonous food, leaking natural gas, smoke, and airborne pollutants. This chapter addresses the influences of neurotoxic exposures on human chemoreception and provides basic information on the adverse influences of such exposures on rodent epithelia. The focus of the chapter is in olfaction, given dearth of empiric research on the effects of neurotoxic chemical exposures on the sense of taste, i...
2015: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/26563792/occupational-exposures-and-parkinsonism
#14
REVIEW
W Michael Caudle
In recent years, the contribution of exposure to environmental toxicants has been recognized as a significant contributor to the etiopathogenesis of parkinsonism. Of these toxicants, exposure to pesticides, metals, solvents used in manufacturing processes, as well as flame-retardant chemicals used in consumer and commercial products, has received the greatest attention as possible risk factors. Related to this, individuals who are exposed to these compounds at high concentrations or for prolonged periods of time in an occupational setting appear to be one of the more vulnerable populations to these effects...
2015: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/26558463/methylmercury-can-induce-parkinson-s-like-neurotoxicity-similar-to-1-methyl-4-phenylpyridinium-a-genomic-and-proteomic-analysis-on-mn9d-dopaminergic-neuron-cells
#15
Yueting Shao, Daniel Figeys, Zhibin Ning, Ryan Mailloux, Hing Man Chan
Exposure to environmental chemicals has been implicated as a possible risk factor for the development of neurodegenerative diseases. Our previous study showed that methylmercury (MeHg) exposure can disrupt synthesis, uptake and metabolism of dopamine similar to 1-methyl-4-phenylpyridinium (MPP(+)). The objective of this study was to investigate the effects of MeHg exposure on gene and protein profiles in a dopaminergic MN9D cell line. MN9D cells were treated with MeHg (1-5 μM) and MPP(+) (10-40 μM) for 48 hr...
December 2015: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/26411940/-oxidative-stress-derived-from-airborne-fine-and-ultrafine-particles-and-the-effects-on-brain-nervous-system-part-2
#16
REVIEW
Masaru Sagai, Tin Tin Win-Shwe
Traffic-related air pollution is a major contributor to urban air pollution. Diesel exhaust (DE) is its most important component of near-road and urban air pollutions and is commonly used as a surrogate model of air pollution in health effects studies. In particular, diesel exhaust particles (DEPs) and nanoparticles in DEPs are the components considered hazardous for health. It is widely known that exposure to DEPs is associated with mortality caused by respiratory and cardiovascular diseases. Recently, evidence has been accumulating showing that DEPs and nanoparticles may cause neurodegenerative disorders...
2015: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
https://www.readbyqxmd.com/read/26109889/younger-age-at-onset-of-sporadic-parkinson-s-disease-among-subjects-occupationally-exposed-to-metals-and-pesticides
#17
Marcia H Ratner, David H Farb, Josef Ozer, Robert G Feldman, Raymon Durso
An earlier age at onset of Parkinson's disease (PD) has been reported to be associated with occupational exposures to manganese and hydrocarbon solvents suggesting that exposure to neurotoxic chemicals may hasten the progression of idiopathic PD. In this study the role of occupational exposure to metals and pesticides in the progression of idiopathic PD was assessed by looking at age at disease onset. The effects of heritable genetic risk factors, which may also influence age at onset, was minimized by including only sporadic cases of PD with no family history of the disease (n=58)...
September 2014: Interdisciplinary Toxicology
https://www.readbyqxmd.com/read/26100754/is-early-life-iron-exposure-critical-in-neurodegeneration
#18
REVIEW
Dominic J Hare, Manish Arora, Nicole L Jenkins, David I Finkelstein, Philip A Doble, Ashley I Bush
The effects of iron deficiency are well documented, but relatively little is known about the long-term implications of iron overload during development. High levels of redox-active iron in the brain have been associated with neurodegenerative disorders, most notably Parkinson disease, yet a gradual increase in brain iron seems to be a feature of normal ageing. Increased brain iron levels might result from intake of infant formula that is excessively fortified with iron, thereby altering the trajectory of brain iron uptake and amplifying the risk of iron-associated neurodegeneration in later life...
September 2015: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/26094596/ambroxol-induced-rescue-of-defective-glucocerebrosidase-is-associated-with-increased-limp-2-and-saposin-c-levels-in-gba1-mutant-parkinson-s-disease-cells
#19
Giulia Ambrosi, Cristina Ghezzi, Roberta Zangaglia, Giovanna Levandis, Claudio Pacchetti, Fabio Blandini
Heterozygous mutations in GBA1 gene, encoding for lysosomal enzyme glucocerebrosidase (GCase), are a major risk factor for sporadic Parkinson's disease (PD). Defective GCase has been reported in fibroblasts of GBA1-mutant PD patients and pharmacological chaperone ambroxol has been shown to correct such defect. To further explore this issue, we investigated GCase and elements supporting GCase function and trafficking in fibroblasts from sporadic PD patients--with or without heterozygous GBA1 mutations--and healthy subjects, in basal conditions and following in vitro exposure to ambroxol...
October 2015: Neurobiology of Disease
https://www.readbyqxmd.com/read/26052547/vulnerability-of-synapses-in-the-frontal-cortex-of-mice-developmentally-exposed-to-an-insecticide-potential-contribution-to-neuropsychiatric-disease
#20
W Michael Caudle
Increasingly, exposure to various chemicals found in our environment has been found to be a significant contributor to the risk of developing neurological disease, such as Parkinson disease, autism spectrum disorder, as well as other deficits in thought and function. Exposure to these compounds during critical periods of neurodevelopment, encompassing exposures that occur in utero, during infancy, childhood, and adolescence, represents a time period of nervous system growth that is uniquely vulnerable to disruption by environmental chemicals...
2015: Neurotransmitter
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