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Parkinson Disease: HELP
Articles by Laura Berkowitz
Based on 2 articles published since 2010
(Why 2 articles?)
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Between 2010 and 2020, L. Berkowitz wrote the following 2 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Article The Small GTPase RAC1/CED-10 Is Essential in Maintaining Dopaminergic Neuron Function and Survival Against α-Synuclein-Induced Toxicity. 2018

Kim, Hanna / Calatayud, Carles / Guha, Sanjib / Fernández-Carasa, Irene / Berkowitz, Laura / Carballo-Carbajal, Iria / Ezquerra, Mario / Fernández-Santiago, Rubén / Kapahi, Pankaj / Raya, Ángel / Miranda-Vizuete, Antonio / Lizcano, Jose Miguel / Vila, Miquel / Caldwell, Kim A / Caldwell, Guy A / Consiglio, Antonella / Dalfo, Esther. ·Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, 35487, USA. · Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital-IDIBELL, 08028, L'Hospitalet de Llobregat, Spain. · Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, 08908, Spain. · Center of Regenerative Medicine in Barcelona (CMRB), Center for Networked Biomedical Research on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Hospital Duran i Reynals, 08908, L'Hospitalet de Llobregat, Spain. · Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945, USA. · Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), 08035, Barcelona, Spain. · Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, Department of Neurology: Clinical and Experimental Research, IDIBAPS - Hospital Clínic de Barcelona, 08036, Barcelona, Spain. · Catalan Institution for Research and Advanced Studies (ICREA), 08010, Barcelona, Spain. · Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/ Universidad de Sevilla, 41013, Sevilla, Spain. · Department of Biochemistry and Molecular Biology, Institut de Neurociències, Faculty of Medicine, M2, Universitat Autònoma de Barcelona (UAB), Bellaterra Campus, Cerdanyola del Vallés, Barcelona, Spain. · Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital-IDIBELL, 08028, L'Hospitalet de Llobregat, Spain. consiglio@ub.edu. · Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, 08908, Spain. consiglio@ub.edu. · Department of Molecular and Translational Medicine, University of Brescia, Brescia, Spain. consiglio@ub.edu. · Department of Biochemistry and Molecular Biology, Institut de Neurociències, Faculty of Medicine, M2, Universitat Autònoma de Barcelona (UAB), Bellaterra Campus, Cerdanyola del Vallés, Barcelona, Spain. esther.dalfo@uab.cat. · Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), Can Baumann, 08500, Vic, Spain. esther.dalfo@uab.cat. ·Mol Neurobiol · Pubmed #29429047.

ABSTRACT: Parkinson's disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to the organization of the actin and microtubule cytoskeletons, has been suggested to participate to Parkinson's disease pathogenesis. Nevertheless, its exact contribution remains obscure. To unveil the participation of the Rho GTPase family to the molecular pathogenesis of Parkinson's disease, we first used C elegans to demonstrate the role of the small GTPase RAC1 (ced-10 in the worm) in maintaining dopaminergic function and survival in the presence of alpha-synuclein. In addition, ced-10 mutant worms determined an increase of alpha-synuclein inclusions in comparison to control worms as well as an increase in autophagic vesicles. We then used a human neuroblastoma cells (M17) stably over-expressing alpha-synuclein and found that RAC1 function decreased the amount of amyloidogenic alpha-synuclein. Further, by using dopaminergic neurons derived from patients of familial LRRK2-Parkinson's disease we report that human RAC1 activity is essential in the regulation of dopaminergic cell death, alpha-synuclein accumulation, participates in neurite arborization and modulates autophagy. Thus, we determined for the first time that RAC1/ced-10 participates in Parkinson's disease associated pathogenesis and established RAC1/ced-10 as a new candidate for further investigation of Parkinson's disease associated mechanisms, mainly focused on dopaminergic function and survival against α-synuclein-induced toxicity.

2 Article Mitochondrial dysfunction, oxidative stress, and neurodegeneration elicited by a bacterial metabolite in a C. elegans Parkinson's model. 2014

Ray, A / Martinez, B A / Berkowitz, L A / Caldwell, G A / Caldwell, K A. ·Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA. · 1] Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA [2] Departments of Neurobiology and Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA. ·Cell Death Dis · Pubmed #24407237.

ABSTRACT: Genetic and idiopathic forms of Parkinson's disease (PD) are characterized by loss of dopamine (DA) neurons and typically the formation of protein inclusions containing the alpha-synuclein (α-syn) protein. Environmental contributors to PD remain largely unresolved but toxins, such as paraquat or rotenone, represent well-studied enhancers of susceptibility. Previously, we reported that a bacterial metabolite produced by Streptomyces venezuelae caused age- and dose-dependent DA neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons. We hypothesized that this metabolite from a common soil bacterium could enhance neurodegeneration in combination with PD susceptibility gene mutations or toxicants. Here, we report that exposure to the metabolite in C. elegans DA neurons expressing human α-syn or LRRK2 G2019S exacerbates neurodegeneration. Using the PD toxin models 6-hydroxydopamine and rotenone, we demonstrate that exposure to more than one environmental risk factor has an additive effect in eliciting DA neurodegeneration. Evidence suggests that PD-related toxicants cause mitochondrial dysfunction, thus we examined the impact of the metabolite on mitochondrial activity and oxidative stress. An ex vivo assay of C. elegans extracts revealed that this metabolite causes excessive production of reactive oxygen species. Likewise, enhanced expression of a superoxide dismutase reporter was observed in vivo. The anti-oxidant probucol fully rescued metabolite-induced DA neurodegeneration, as well. Interestingly, the stress-responsive FOXO transcription factor DAF-16 was activated following exposure to the metabolite. Through further mechanistic analysis, we discerned the mitochondrial defects associated with metabolite exposure included adenosine triphosphate impairment and upregulation of the mitochondrial unfolded protein response. Metabolite-induced toxicity in DA neurons was rescued by complex I activators. RNA interference (RNAi) knockdown of mitochondrial complex I subunits resulted in rescue of metabolite-induced toxicity in DA neurons. Taken together, our characterization of cellular responses to the S. venezuelae metabolite indicates that this putative environmental trigger of neurotoxicity may cause cell death, in part, through mitochondrial dysfunction and oxidative stress.