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Department of Chemistry & Biochemistry

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Browsing Department of Chemistry & Biochemistry by Author "Albert Einstein College of Medicine"

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    The effects of pdr1, djr1.1 and pink1 loss in manganese-induced toxicity and the role of alpha-synuclein in C-elegans
    (Royal Society of Chemistry, 2014) Bornhorst, Julia; Chakraborty, Sudipta; Meyer, Soeren; Lohren, Hanna; Brinkhaus, Sigrid Grosse; Knight, Adam L.; Caldwell, Kim A.; Caldwell, Guy A.; Karst, Uwe; Schwerdtle, Tanja; Bowman, Aaron; Aschner, Michael; University of Munster; Vanderbilt University; University of Alabama Tuscaloosa; Yeshiva University; Albert Einstein College of Medicine
    Parkinson's disease (PD) is a neurodegenerative brain disorder characterized by selective dopaminergic (DAergic) cell loss that results in overt motor and cognitive deficits. Current treatment options exist to combat PD symptomatology, but are unable to directly target its pathogenesis due to a lack of knowledge concerning its etiology. Several genes have been linked to PD, including three genes associated with an early-onset familial form: parkin, pink1 and dj1. All three genes are implicated in regulating oxidative stress pathways. Another hallmark of PD pathophysiology is Lewy body deposition, associated with the gain-of-function genetic risk factor a-synuclein. The function of a-synuclein is poorly understood, as it shows both neurotoxic and neuroprotective activities in PD. Using the genetically tractable invertebrate Caenorhabditis elegans (C. elegans) model system, the neurotoxic or neuroprotective role of a-synuclein upon acute Mn exposure in the background of mutated pdr1, pink1 or djr1.1 was examined. The pdr1 and djr1.1 mutants showed enhanced Mn accumulation and oxidative stress that was reduced by a-synuclein. Moreover, DAergic neurodegeneration, while unchanged with Mn exposure, returned to wild-type (WT) levels for pdr1, but not djr1.1 mutants expressing a-synuclein. Taken together, this study uncovers a novel, neuroprotective role for WT human a-synuclein in attenuating Mn-induced toxicity in the background of PD-associated genes, and further supports the role of extracellular dopamine in exacerbating Mn neurotoxicity.
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    The Time Is Right to Focus on Model Organism Metabolomes
    (MDPI, 2016) Edison, Arthur S.; Hall, Robert D.; Junot, Christophe; Karp, Peter D.; Kurland, Irwin J.; Mistrik, Robert; Reed, Laura K.; Saito, Kazuki; Salek, Reza M.; Steinbeck, Christoph; Sumner, Lloyd W.; Viant, Mark R.; University of Georgia; Wageningen University & Research; CEA; UDICE-French Research Universities; Universite Paris Saclay; SRI International; Yeshiva University; Albert Einstein College of Medicine; University of Alabama Tuscaloosa; RIKEN; Chiba University; Wellcome Trust Sanger Institute; European Molecular Biology Laboratory (EMBL); University of Missouri Columbia; University of Birmingham
    Model organisms are an essential component of biological and biomedical research that can be used to study specific biological processes. These organisms are in part selected for facile experimental study. However, just as importantly, intensive study of a small number of model organisms yields important synergies as discoveries in one area of science for a given organism shed light on biological processes in other areas, even for other organisms. Furthermore, the extensive knowledge bases compiled for each model organism enable systems-level understandings of these species, which enhance the overall biological and biomedical knowledge for all organisms, including humans. Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i. e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research.