Mark R Cookson

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP
    M Emdadul Haque
    Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, Ottawa, ON, Canada
    Proc Natl Acad Sci U S A 105:1716-21. 2008
  2. ncbi request reprint Cellular effects of LRRK2 mutations
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD 20892 3707, USA
    Biochem Soc Trans 40:1070-3. 2012
  3. pmc Integration of GWAS SNPs and tissue specific expression profiling reveal discrete eQTLs for human traits in blood and brain
    Dena G Hernandez
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892 3707, USA
    Neurobiol Dis 47:20-8. 2012
  4. pmc Mitochondrial alterations in PINK1 deficient cells are influenced by calcineurin-dependent dephosphorylation of dynamin-related protein 1
    Anna Sandebring
    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, United States of America
    PLoS ONE 4:e5701. 2009
  5. pmc mRNA expression, splicing and editing in the embryonic and adult mouse cerebral cortex
    Allissa A Dillman
    Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Nat Neurosci 16:499-506. 2013
  6. pmc Post-translational decrease in respiratory chain proteins in the Polg mutator mouse brain
    David N Hauser
    Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America Brown University National Institutes of Health Graduate Partnership Program, Department of Neuroscience, Brown University, Providence, Rhode Island, United States of America
    PLoS ONE 9:e94646. 2014
  7. doi request reprint Evolution of neurodegeneration
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892 3707, USA
    Curr Biol 22:R753-61. 2012
  8. pmc Parkinsonism due to mutations in PINK1, parkin, and DJ-1 and oxidative stress and mitochondrial pathways
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Cold Spring Harb Perspect Med 2:a009415. 2012
  9. pmc Gene expression in the Parkinson's disease brain
    Patrick A Lewis
    Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
    Brain Res Bull 88:302-12. 2012
  10. pmc Evidence for natural antisense transcript-mediated inhibition of microRNA function
    Mohammad Ali Faghihi
    Department of Neuroscience, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA
    Genome Biol 11:R56. 2010

Detail Information

Publications104 found, 100 shown here

  1. pmc Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP
    M Emdadul Haque
    Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, Ottawa, ON, Canada
    Proc Natl Acad Sci U S A 105:1716-21. 2008
    ..Thus, our findings indicate that Pink1 plays a functional role in the survival of neurons and that cytoplasmic targets, in addition to its other actions in the mitochondria, may be important for this protective effect...
  2. ncbi request reprint Cellular effects of LRRK2 mutations
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD 20892 3707, USA
    Biochem Soc Trans 40:1070-3. 2012
    ..The relevance of these phenotypes for PD is not yet clear, and a great deal of work is needed to understand them in more depth...
  3. pmc Integration of GWAS SNPs and tissue specific expression profiling reveal discrete eQTLs for human traits in blood and brain
    Dena G Hernandez
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892 3707, USA
    Neurobiol Dis 47:20-8. 2012
    ..These observations suggest that design of eQTL mapping experiments should consider tissue of interest for the disease or other traits studied...
  4. pmc Mitochondrial alterations in PINK1 deficient cells are influenced by calcineurin-dependent dephosphorylation of dynamin-related protein 1
    Anna Sandebring
    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, United States of America
    PLoS ONE 4:e5701. 2009
    ..We propose that alterations in mitochondrial connectivity in this system are secondary to functional effects on mitochondrial membrane potential...
  5. pmc mRNA expression, splicing and editing in the embryonic and adult mouse cerebral cortex
    Allissa A Dillman
    Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Nat Neurosci 16:499-506. 2013
    ..We provide this data set and analysis as a resource for understanding gene expression in the embryonic and adult cerebral cortex...
  6. pmc Post-translational decrease in respiratory chain proteins in the Polg mutator mouse brain
    David N Hauser
    Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America Brown University National Institutes of Health Graduate Partnership Program, Department of Neuroscience, Brown University, Providence, Rhode Island, United States of America
    PLoS ONE 9:e94646. 2014
    ..However, we found no evidence that the changes we observed in protein levels were the result of decreases in mRNA expression. These results show that there are post-translational effects associated with mutations in Polg...
  7. doi request reprint Evolution of neurodegeneration
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892 3707, USA
    Curr Biol 22:R753-61. 2012
    ....
  8. pmc Parkinsonism due to mutations in PINK1, parkin, and DJ-1 and oxidative stress and mitochondrial pathways
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Cold Spring Harb Perspect Med 2:a009415. 2012
    ..Work in progress in the field is aimed at understanding these relationships in more depth...
  9. pmc Gene expression in the Parkinson's disease brain
    Patrick A Lewis
    Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
    Brain Res Bull 88:302-12. 2012
    ..In this review, we will summarise current state of gene expression studies of the brain in Parkinson's disease, and examine how these techniques can be used to gain an insight into aetiology of this devastating disorder...
  10. pmc Evidence for natural antisense transcript-mediated inhibition of microRNA function
    Mohammad Ali Faghihi
    Department of Neuroscience, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA
    Genome Biol 11:R56. 2010
    ..The BACE1-antisense transcript is markedly up-regulated in brain samples from Alzheimer's disease patients and promotes the stability of the (sense) BACE1 transcript...
  11. pmc Alpha-synuclein overexpression increases dopamine toxicity in BE2-M17 cells
    Marco Bisaglia
    Department of Biology, University of Padova, 35121 Padova, Italy
    BMC Neurosci 11:41. 2010
    ....
  12. ncbi request reprint How genetics research in Parkinson's disease is enhancing understanding of the common idiopathic forms of the disease
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20982 3707, USA
    Curr Opin Neurol 18:706-11. 2005
    ..The subject of this review is to highlight these discoveries and to discuss their relationships to idiopathic Parkinson's disease...
  13. ncbi request reprint Hero versus antihero: the multiple roles of alpha-synuclein in neurodegeneration
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA
    Exp Neurol 199:238-42. 2006
  14. ncbi request reprint The biochemistry of Parkinson's disease
    Mark R Cookson
    Cell Biology Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland 20892, USA
    Annu Rev Biochem 74:29-52. 2005
    ..However, we have not yet fully resolved how the recessive genes relate to alpha-synuclein, or whether they represent different ways to induce a similar phenotype...
  15. pmc Aging--RNA in development and disease
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
    Wiley Interdiscip Rev RNA 3:133-43. 2012
    ....
  16. ncbi request reprint A feedforward loop links Gaucher and Parkinson's diseases?
    Mark R Cookson
    Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD 20892 3707, USA
    Cell 146:9-11. 2011
    ..2011) uncover a possible mechanism to explain this connection: loss of glucocerebrosidase creates a positive feedback loop of reduced lysosomal function and α-synuclein accumulation, ultimately leading to neurodegeneration...
  17. pmc Molecules that cause or prevent Parkinson's disease
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    PLoS Biol 2:e401. 2004
  18. ncbi request reprint The roles of kinases in familial Parkinson's disease
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland 20892 3707, USA
    J Neurosci 27:11865-8. 2007
    ....
  19. ncbi request reprint The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health NIH, Building 35, Room 1A116, MSC 3707, 35 Convent Drive, Bethesda, Maryland 20982 3707, USA
    Nat Rev Neurosci 11:791-7. 2010
    ..These concepts can be used to understand disease processes and to develop therapeutic opportunities for the treatment of Parkinson's disease...
  20. ncbi request reprint Neurodegeneration: how does parkin prevent Parkinson's disease?
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, NIH, Bldg 10, Room 6C103, MSC1589, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Curr Biol 13:R522-4. 2003
    ..Recent data suggest we may be beginning to understand the nature of the proteins that are targeted by Parkin and how these cause neuronal damage...
  21. ncbi request reprint Parkin's substrates and the pathways leading to neuronal damage
    Mark R Cookson
    Laboratory of Neurogenetics National Institute on Agins, NIH, Bethesda, MD 20892, USA
    Neuromolecular Med 3:1-13. 2003
    ..The possibility that loss of regulation of turnover of one or more of these substrates contributes to the selective neurodegeneration seen in PD is also discussed...
  22. pmc Parkinson's disease: insights from pathways
    Mark R Cookson
    National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
    Hum Mol Genet 19:R21-7. 2010
    ..Collectively, these results highlight how understanding pathways for inherited PD are starting to impact ideas about the pathogenesis, some of which may also be relevant to the commoner sporadic disease...
  23. pmc Crystallizing ideas about Parkinson's disease
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 10, Room 6C103, MSC1589, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 100:9111-3. 2003
  24. pmc Cell systems and the toxic mechanism(s) of alpha-synuclein
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20982 3707, USA
    Exp Neurol 209:5-11. 2008
    ..In this article, we develop a framework for thinking about alpha-synuclein in terms of initiating events and secondary processes that are required to trigger neuronal dysfunction and cell death...
  25. pmc Unravelling the role of defective genes
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
    Prog Brain Res 183:43-57. 2010
    ..Examples will be given of both recessive and dominant genes for parkinsonism, showing how the analysis of multiple gene mutations can be a powerful approach for dissecting out which function(s) are important for the disease process...
  26. pmc DJ-1, PINK1, and their effects on mitochondrial pathways
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, Maryland 20982 3707, USA
    Mov Disord 25:S44-8. 2010
    ..In this short review, I will discuss how we can use some of this information to understand why it is that neurons become dysfunctional in PD...
  27. pmc alpha-Synuclein and neuronal cell death
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, NIH, Building 35, Room 1A116, MSC 3707, 35 Convent Drive, Bethesda, MD 20982 3707, USA
    Mol Neurodegener 4:9. 2009
    ..Finally, the therapeutic implications of toxicity of alpha-synuclein will be discussed...
  28. ncbi request reprint Pathways to Parkinsonism
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Neuron 37:7-10. 2003
    ..The identification of multiple genetic causes will provide further impetus to describe the pathway leading to PD...
  29. pmc The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation
    Elisa Greggio
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, NIA, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 283:16906-14. 2008
    ..Finally, we demonstrate that LRRK2 undergoes intramolecular autophosphorylation. Together, these results provide insight into the mechanism and regulation of LRRK2 kinase activity...
  30. ncbi request reprint Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1
    Elisa Greggio
    Cell Biology and Gene Expression Unit, National Institute on Aging, Bethesda, Maryland 20982 3707, USA
    J Neurochem 102:93-102. 2007
    ..We show that mutations in dardarin are more prone to form inclusion bodies in transfected cells and are more toxic than equivalent mutations in LRRK1. This work suggests that dardarin/LRRK2 is inherently more damaging than LRRK1...
  31. pmc The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2
    Lizhen Wang
    Unit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland 20892, USA
    J Neurosci 28:3384-91. 2008
    ..Therefore, inhibition of LRRK2 kinase activity can be achieved by blocking Hsp90-mediated chaperone activity and Hsp90 inhibitors may serve as potential anti-PD drugs...
  32. ncbi request reprint Effects of DJ-1 mutations and polymorphisms on protein stability and subcellular localization
    Jeff Blackinton
    Laboratory of Neurogenetics, National Institute on Aging, NIH, Building 10 Room 6C103, MSC1589 9000 Rockville Pike, Bethesda, MD 20892, USA
    Brain Res Mol Brain Res 134:76-83. 2005
    ..However, in all cases, the proportion of cells with mitochondrial DJ-1 staining was increased in oxidative conditions, suggesting that oxidation promotes the mitochondrial localization of DJ-1...
  33. pmc DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy
    Kelly Jean Thomas
    Laboratory of Neurogenetics, National Institute on Aging, Flow Cytometry Core Facility, National Institutes of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20982 3707, USA
    Hum Mol Genet 20:40-50. 2011
    ..None of the three proteins complex together using size exclusion chromatography. These data suggest that DJ-1 works in parallel to the PINK1/parkin pathway to maintain mitochondrial function in the presence of an oxidative environment...
  34. pmc RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways
    Marcel P van der Brug
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD 20892 3707, USA
    Proc Natl Acad Sci U S A 105:10244-9. 2008
    ..These data implicate a single mechanism for the pleiotropic effects of DJ-1 in different model systems, namely that the protein binds multiple RNA targets in an oxidation-dependent manner...
  35. ncbi request reprint L166P mutant DJ-1, causative for recessive Parkinson's disease, is degraded through the ubiquitin-proteasome system
    David W Miller
    Laboratory of Neurogenetics, NIA, National Institutes of Health, Bethesda, Maryland 20892 1589, USA
    J Biol Chem 278:36588-95. 2003
    ..These observations are reminiscent of other recessive gene mutations that produce an effective loss of function. The L166P mutation has the simple effect of promoting DJ-1 degradation, thereby reducing net DJ-1 protein within the cell...
  36. pmc The R1441C mutation of LRRK2 disrupts GTP hydrolysis
    Patrick A Lewis
    Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD 20892 3707, USA
    Biochem Biophys Res Commun 357:668-71. 2007
    ..We show that LRRK2 immunoprecipitated from cells has a detectable GTPase activity that is disrupted by a familial mutation associated with PD located within the GTPase domain, R1441C...
  37. doi request reprint The G2385R variant of leucine-rich repeat kinase 2 associated with Parkinson's disease is a partial loss-of-function mutation
    Iakov N Rudenko
    Cell Biology and Gene Expression Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Biochem J 446:99-111. 2012
    ..These results may be important in understanding the differing mechanism(s) by which mutations in LRRK2 act and may also have implications for therapeutic strategies for PD...
  38. pmc Formation of a stabilized cysteine sulfinic acid is critical for the mitochondrial function of the parkinsonism protein DJ-1
    Jeff Blackinton
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, NIA, National Institutes of Health, Bethesda, Maryland 20892 3707, USA
    J Biol Chem 284:6476-85. 2009
    ..We therefore conclude that formation of Cys106-sulfinic acid is a key modification that regulates the protective function of DJ-1...
  39. pmc Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability
    Alexandra Beilina
    Laboratory of Neurogenetics, National Institute on Aging NIH, 35 Convent Drive, Bethesda, MD 20892 3707, USA
    Proc Natl Acad Sci U S A 102:5703-8. 2005
    ..The physiological relevance of this observation is not yet clear, but it implies that a portion of PINK1 may be exported after processing in the mitochondria...
  40. pmc The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization
    Rosa M Canet-Aviles
    Laboratory of Neurogenetics, National Institute on Aging, 9000 Rockville Pike, Bethesda, MD 20892 1589, USA
    Proc Natl Acad Sci U S A 101:9103-8. 2004
    ..We suggest that DJ-1 protects against neuronal death, and that this is signaled by acidification of the key cysteine residue, C106...
  41. pmc Distinct DNA methylation changes highly correlated with chronological age in the human brain
    Dena G Hernandez
    Laboratory of Neurogenetics, National Institute on Aging, Baltimore, MD 20892, USA
    Hum Mol Genet 20:1164-72. 2011
    ..This suggests that specific age-related DNA methylation changes may have quite a broad impact on gene expression in the human brain...
  42. ncbi request reprint DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA
    Sarah Camargos
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA
    Lancet Neurol 7:207-15. 2008
    ..Dystonia and parkinsonism may present as part of the same genetic disorder. Identification of the genetic mutations that underlie these diseases may help to shed light on the aetiological processes involved...
  43. pmc The Parkinson's disease associated LRRK2 exhibits weaker in vitro phosphorylation of 4E-BP compared to autophosphorylation
    Azad Kumar
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 5:e8730. 2010
    ..Overall, our results suggest that 4E-BP is a relatively poor direct substrate for LRRK2...
  44. ncbi request reprint Kinase activity is required for the toxic effects of mutant LRRK2/dardarin
    Elisa Greggio
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892 3707, USA
    Neurobiol Dis 23:329-41. 2006
    ..We also show that dardarin protein is expressed within human midbrain neurons and that C-terminal epitopes are also found in some Lewy bodies...
  45. pmc Amyotrophic lateral sclerosis 2-deficiency leads to neuronal degeneration in amyotrophic lateral sclerosis through altered AMPA receptor trafficking
    Chen Lai
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892 3707, USA
    J Neurosci 26:11798-806. 2006
    ....
  46. pmc Post-transcriptional regulation of mRNA associated with DJ-1 in sporadic Parkinson disease
    Jeff Blackinton
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States
    Neurosci Lett 452:8-11. 2009
    ..These results suggest that these proteins undergo regulation at the post-transcriptional level that may involve translational regulation by DJ-1...
  47. ncbi request reprint 14-3-3 proteins are promising LRRK2 interactors
    Iakov N Rudenko
    Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20982 3707, USA
    Biochem J 430:e5-6. 2010
    ..Collectively, these new results identify a potentially important regulatory mechanism of this complex protein and might provide ways to think about therapeutic opportunities for PD...
  48. ncbi request reprint Genetics of Parkinson's disease and parkinsonism
    John Hardy
    Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, 35 Convent Drive, Bethesda, MD 20892, USA
    Ann Neurol 60:389-98. 2006
    ....
  49. pmc Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease
    Alexandria Beilina
    Cell Biology and Gene Expression Section, Computational Biology Core, Laboratory of Neurogenetics, and Molecular Genetics Section, National Institute on Aging National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 111:2626-31. 2014
    ..We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms. ..
  50. pmc Age-associated changes in gene expression in human brain and isolated neurons
    Azad Kumar
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892 3707, USA
    Neurobiol Aging 34:1199-209. 2013
    ..Overall, our results show that there is a distinct and reproducible gene signature for aging in the human brain...
  51. pmc Genome-wide association study reveals genetic risk underlying Parkinson's disease
    Javier Simon-Sanchez
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Nat Genet 41:1308-12. 2009
    ..14, P = 1.55 x 10(-5)). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease...
  52. pmc Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies
    Gaia Skibinski
    Gladstone Institute of Neurological Disease, the Taube Koret Center for Neurodegenerative Disease Research, and the Hellman Family Foundation Program in Alzheimer s Disease Research, San Francisco, California 94158, Departments of Neurology, Physiology, and Graduate Programs in Neuroscience and Biomedical Sciences, University of California, San Francisco, California 94158, and Laboratory of Neurogenetics, National Institutes of Health, Bethesda, Maryland 20892
    J Neurosci 34:418-33. 2014
    ..These findings suggest that LRRK2 levels are more important than kinase activity per se in predicting toxicity and implicate synuclein as a major mediator of LRRK2-induced neurodegeneration. ..
  53. pmc DJ-1 regulation of mitochondrial function and autophagy through oxidative stress
    Melissa K McCoy
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
    Autophagy 7:531-2. 2011
    ....
  54. doi request reprint Mechanisms in dominant parkinsonism: The toxic triangle of LRRK2, alpha-synuclein, and tau
    Jean Marc Taymans
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, NIA, National Institutes of Health, Bethesda, MD 20892 3707, USA
    Bioessays 32:227-35. 2010
    ..We discuss the potential relationship between these genes and suggest a model for PD pathogenesis where LRRK2 is upstream of pathogenic effects through SNCA, tau, or both proteins...
  55. ncbi request reprint RING finger 1 mutations in Parkin produce altered localization of the protein
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Hum Mol Genet 12:2957-65. 2003
    ..We have replicated this observation in primary cultured neurons and demonstrate, by the accumulation/co-localization of cytoskeletal protein vimentin, that the inclusion bodies are aggresomes, a cellular response to misfolded protein...
  56. pmc The Parkinson's disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites
    Elisa Greggio
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892 3707, USA
    Biochem Biophys Res Commun 389:449-54. 2009
    ..These data suggest that the kinase and GTPase activities of LRRK2 may exhibit complex autoregulatory interdependence...
  57. pmc Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain
    J Raphael Gibbs
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Genet 6:e1000952. 2010
    ..We believe these data, which we have made publicly available, will provide a critical step toward understanding the biological effects of genetic variation...
  58. pmc Emerging pathways in genetic Parkinson's disease: Potential role of ceramide metabolism in Lewy body disease
    Jose Bras
    Molecular Genetics Unit, National Institutes on Aging, Bethesda, MD, USA
    FEBS J 275:5767-73. 2008
    ..Doing this, we suggest that several of the genes involved in disparate Lewy body diseases impinge on ceramide metabolism and we suggest that this may be a common theme for pathogenesis...
  59. pmc Cell population-specific expression analysis of human cerebellum
    Alexandre Kuhn
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
    BMC Genomics 13:610. 2012
    ..This procedure makes use of marker gene expression and circumvents the need for additional experimental information like tissue composition...
  60. ncbi request reprint Parkin and alpha-synuclein: opponent actions in the pathogenesis of Parkinson's disease
    Melisa J Baptista
    Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA
    Neuroscientist 10:63-72. 2004
    ..The authors will also discuss ways in which to test some of these ideas, by using newly identified genes such as DJ-1 that cause similar phenotypes...
  61. ncbi request reprint Unaltered alpha-synuclein blood levels in juvenile Parkinsonism with a parkin exon 4 deletion
    David W Miller
    Laboratory of Neurogenetics, NIA, National Institutes of Health, Bldg 35, Rm 1A 100, 35 Convent Drive, Bethesda, MD 20892, USA
    Neurosci Lett 374:189-91. 2005
    ..We find there is not and discuss this result in terms of the putative relationships between alpha-synuclein and parkin...
  62. ncbi request reprint Co-ordinate transcriptional regulation of dopamine synthesis genes by alpha-synuclein in human neuroblastoma cell lines
    Melisa J Baptista
    Laboratory of Neurogenetics, National Institute on Aging NIH, Building 10 Room 6C103, MSC 1589, 9000 Rockville Pike, Bethesda, MD 20892, USA
    J Neurochem 85:957-68. 2003
    ..Reduced expression of the orphan nuclear receptor Nurr1 was also noted, suggesting that the co-ordinate regulation of dopamine synthesis is regulated through this transcription factor...
  63. pmc Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis
    Janel O Johnson
    1 Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 2
    Nat Neurosci 17:664-6. 2014
    ..We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration. ..
  64. ncbi request reprint Identification of the epitope of a monoclonal antibody to DJ-1
    David W Miller
    Laboratory of Neurogenetics, National Institute on Aging, Bldg 35, Rm 1A 1002, 35 Convent Drive, Bethesda, MD 20892, USA
    Neurosci Lett 374:203-6. 2005
    ..Moreover, the loss of immunoreactivity due to such a small substitution demonstrates the remarkable sensitivity of the monoclonal antibody 3E8 to DJ-1...
  65. pmc Arsenite Stress Down-regulates Phosphorylation and 14-3-3 Binding of Leucine-rich Repeat Kinase 2 (LRRK2), Promoting Self-association and Cellular Redistribution
    Adamantios Mamais
    From the Reta Lila Weston Institute of Neurological Studies, University College London Institute of Neurology, London WC1N 1PJ, United Kingdom, the Department of Molecular Neuroscience, University College London Institute of Neurology, London WC1N 3BJ, United Kingdom, the Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, NIA, National Institutes of Health, Bethesda, Maryland 20892
    J Biol Chem 289:21386-400. 2014
    ..Our data indicate that signaling events induced by arsenite and oxidative stress may regulate LRRK2 function. ..
  66. pmc Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD
    Parastoo Momeni
    Laboratory of Neurogenetics, National Institute of Aging, NIH, Bethesda, MD, USA
    BMC Neurol 6:44. 2006
    ..A new locus for amyotrophic lateral sclerosis--frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p...
  67. pmc PINK1 is selectively stabilized on impaired mitochondria to activate Parkin
    Derek P Narendra
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    PLoS Biol 8:e1000298. 2010
    ..In addition, they support a novel model for the negative selection of damaged mitochondria, in which PINK1 signals mitochondrial dysfunction to Parkin, and Parkin promotes their elimination...
  68. pmc The role of PTEN-induced kinase 1 in mitochondrial dysfunction and dynamics
    Kelly Jean Thomas
    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Int J Biochem Cell Biol 41:2025-35. 2009
    ..This review highlights the role of the mitochondrial kinase, PINK1, in protection against mitochondrial dysfunction and how this might relate to loss of substantia nigra neurons in recessive parkinsonism...
  69. pmc Genetic comorbidities in Parkinson's disease
    Mike A Nalls
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
    Hum Mol Genet 23:831-41. 2014
    ..We show a strong genetically defined level of comorbidity between PD and Crohn's disease as well as between PD and schizophrenia, with likely functional consequences of associated variants occurring in brain. ..
  70. pmc Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans
    Joyce van de Leemput
    Molecular Genetics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Genet 3:e108. 2007
    ..We show here that heterozygous deletion of the 5' part of the ITPR1 gene, encompassing exons 1-10, 1-40, and 1-44 in three studied families, underlies SCA15 in humans...
  71. doi request reprint Role of LRRK2 kinase dysfunction in Parkinson disease
    Azad Kumar
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892 3707, USA
    Expert Rev Mol Med 13:e20. 2011
    ..Recent work has focused on the kinase and GTP-binding domains of LRRK2, and it is assumed that these will be therapeutically important, although there is a substantial amount of work to be done to address this hypothesis...
  72. ncbi request reprint Dystonia and the nuclear envelope
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA
    Neuron 48:875-7. 2005
    ..The experiments also highlight the possible role of nuclear envelope dynamics in maintaining normal neuronal function...
  73. ncbi request reprint Microarray analysis reveals induction of heat shock proteins mRNAs by the torsion dystonia protein, TorsinA
    Melisa J Baptista
    Laboratory of Neurogenetics, National Institute on Aging National Institutes of Health, 9000 Rockville Pike, Building 10, Room 6C103, MSC1589, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Neurosci Lett 343:5-8. 2003
    ..However, both wild type and mutant torsinA were affected to a similar extent, suggesting that this is not related to either disease state or the formation of ER-derived inclusions...
  74. pmc Mitochondrial quality control and dynamics in Parkinson's disease
    Melissa K McCoy
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Antioxid Redox Signal 16:869-82. 2012
    ..Studies of sporadic cases, toxin models, and genetic causes of Parkinson's disease suggest that mitochondrial dysfunction may be an early feature of pathogenesis...
  75. pmc Deep sequencing of coding and non-coding RNA in the CNS
    Marcel Van Der Brug
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA
    Brain Res 1338:146-54. 2010
    ..We will discuss how deep sequencing methods are being applied to characterization of gene expression in the brain and how these technologies might develop over the next few years...
  76. pmc Evolutionary and functional relationships within the DJ1 superfamily
    Sourav Bandyopadhyay
    Laboratory of Neurogenetics, National Institute on Aging, 9000 Rockville Pike, Bethesda, MD 20892, USA
    BMC Evol Biol 4:6. 2004
    ..In this study we looked at sequence homology between members of the DJ-1/ThiJ/PfpI superfamily, which includes a human protein of unclear function, DJ-1, associated with inherited Parkinson's disease...
  77. ncbi request reprint Genes and parkinsonism
    John Hardy
    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Lancet Neurol 2:221-8. 2003
    ..In this review we describe the molecular genetics of PD as currently understood to help explain the pathways that underlie neurodegeneration...
  78. pmc Is inhibition of kinase activity the only therapeutic strategy for LRRK2-associated Parkinson's disease?
    Iakov N Rudenko
    Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Room 1A 116, Bethesda, MD 20892 3707, USA
    BMC Med 10:20. 2012
    ..We also discuss non-kinase-based therapeutic strategies for LRRK2-associated PD as it is possible that different approaches may be needed for different mutations...
  79. ncbi request reprint The persistence of memory
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
    N Engl J Med 355:2697-8. 2006
  80. ncbi request reprint Dominant torsinA mutations in cellular systems
    Melisa J Baptista
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Adv Neurol 94:73-8. 2004
  81. pmc Aggregation of α-synuclein in brain samples from subjects with glucocerebrosidase mutations
    Jae hyuk Choi
    Section on Molecular Neurogenetics, Medical Genetics Branch, NHGRI, National Institutes of Health, Bethesda, MD, USA
    Mol Genet Metab 104:185-8. 2011
    ..Thus, brains from patients with GBA1-associated parkinsonism show biochemical characteristics typical of Lewy body disorders...
  82. ncbi request reprint Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma
    Omar M A El-Agnaf
    Department of Biological Sciences, Lancaster University, Lancaster LA1 4YQ, UK
    FASEB J 17:1945-7. 2003
    ..The detection of extracellular alpha-syn and/or its modified forms in body fluids, particularly in human plasma, offers new opportunities for the development of diagnostic tests for PD and related diseases...
  83. ncbi request reprint Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease
    Frank P Marx
    Department of Neurology, Laboratory of Neurodegeneration, University of Tubingen, Tubingen, Germany
    Hum Mol Genet 12:1223-31. 2003
    ....
  84. ncbi request reprint Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons
    Leonard Petrucelli
    Neurogenetics Laboratory, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA
    Neuron 36:1007-19. 2002
    ..Therefore, parkin and alpha-synuclein are linked by common effects on a pathway associated with selective cell death in catecholaminergic neurons...
  85. ncbi request reprint Selective loss of neurofilament expression in Cu/Zn superoxide dismutase (SOD1) linked amyotrophic lateral sclerosis
    Fiona M Menzies
    Academic Neurology Unit and Academic Unit of Pathology, The Medical School, University of Sheffield, South Yorkshire, UK
    J Neurochem 82:1118-28. 2002
    ..These data suggest that NFL mRNA reductions are common to SALS and FALS patients, and that cells and mice expressing mutant SOD1 may enable us to characterize the molecular mechanism(s) responsible for the loss of neurofilament mRNA...
  86. ncbi request reprint Cu/Zn superoxide dismutase (SOD1) mutations associated with familial amyotrophic lateral sclerosis (ALS) affect cellular free radical release in the presence of oxidative stress
    Mark R Cookson
    Academic Neurology Unit, University of Sheffield, UK
    Amyotroph Lateral Scler Other Motor Neuron Disord 3:75-85. 2002
    ..Theoretically, there are arguments to suggest that NO may exert an important role in motor neuron injury, but there is relatively little direct experimental support for this hypothesis...
  87. ncbi request reprint An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage
    Todd B Sherer
    Center for Neurodegenerative Disease and Department of Neurology, Emory University, Atlanta, Georgia 30322, USA
    J Neurosci 22:7006-15. 2002
    ....
  88. ncbi request reprint Differential gene expression in a cell culture model of SOD1-related familial motor neurone disease
    Janine Kirby
    Academic Neurology Unit, University of Sheffield, School of Medicine and Biomedical Sciences, Beech Hill Road, Sheffield S10 2RX, UK
    Hum Mol Genet 11:2061-75. 2002
    ....
  89. ncbi request reprint Normal localization of deltaF323-Y328 mutant torsinA in transfected human cells
    Casey O'Farrell
    Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Neurosci Lett 327:75-8. 2002
    ..This data suggests that the formation of intracellular inclusions is specific to deltaE302/303 and not a property shared by deltaF323-Y328...
  90. ncbi request reprint Intersecting pathways to neurodegeneration in Parkinson's disease: effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system
    Ranjita Betarbet
    Center for Neurodegenerative Disease, Center for Neurodegenerative Diseases, Whitehead Biomedical Research Building, 615 Michael Street, Atlanta, GA 30322, USA
    Neurobiol Dis 22:404-20. 2006
    ....
  91. ncbi request reprint Sequence conservation between mouse and human synphilin-1
    Casey O'Farrell
    Neurogenetics Laboratory, Mayo Clinic Jacksonville, FL 32224, USA
    Neurosci Lett 322:9-12. 2002
    ..Expression of mouse synphilin-1 across tissues is similar to its human counterpart and not limited to brain. The results show that the synphilin-1 sequence and expression patterns are conserved across species...
  92. ncbi request reprint The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease
    Rina Bandopadhyay
    Reta Lila Weston Institute of Neurological Studies, Royal Free and UCL Medical School, 46 Cleveland Street, London W1T 4JF, UK
    Brain 127:420-30. 2004
    ..These results are consistent with the hypothesis that neuronal-glial interactions are important in the pathophysiology of Parkinson's disease...
  93. pmc Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase
    Junpeng Deng
    Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078, USA
    Proc Natl Acad Sci U S A 105:1499-504. 2008
    ..The structure of the LRRK2 ROC domain also represents a signature from a previously undescribed class of GTPases from complex proteins and results may provide a unique molecular target for therapeutics in PD...
  94. ncbi request reprint Expression of PINK1 mRNA in human and rodent brain and in Parkinson's disease
    Jeff G Blackinton
    Department of Neuroscience, Karolinska Institute, Retzius vag 8, 171 77, Stockholm, Sweden
    Brain Res 1184:10-6. 2007
    ..We also show that PINK1 mRNA expression is similar in nigral neurons from neurologically normal controls and sporadic Parkinson's disease cases...
  95. ncbi request reprint The metalloprotease inhibitor TIMP-3 regulates amyloid precursor protein and apolipoprotein E receptor proteolysis
    HYANG SOOK HOE
    Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057 1464, USA
    J Neurosci 27:10895-905. 2007
    ..TIMP-3 protein levels were increased in human Alzheimer's disease (AD) brain and in APP transgenic mice, suggesting that increased levels of TIMP-3 in AD may contribute to higher levels of Abeta...
  96. ncbi request reprint Neurons inflict self-harm
    Mark R Cookson
    Nat Med 11:1159-61. 2005
  97. ncbi request reprint Development, characterisation and epitope mapping of novel monoclonal antibodies for DJ-1 (PARK7) protein
    Rina Bandopadhyay
    Reta Lila Weston Institute of Neurological Studies, Royal Free and UCL Medical School, The Windeyer Building, 46, Cleveland Street, London W1T 4JF, UK
    Neurosci Lett 383:225-30. 2005
    ..These antibodies could be exploited as important tools in dissecting out DJ-1 expression in different species and examination of the role of DJ-1 in Parkinson's disease...
  98. ncbi request reprint Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson's disease
    Elisa Greggio
    Department of Biology, University of Padova, Padova, Italy
    J Neurochem 93:246-56. 2005
    ..This argues against a strong genetic association between tyrosinase and PD, although the observed contribution to cellular toxicity suggests that a biochemical association is likely...
  99. ncbi request reprint Roles of the proteasome in neurodegenerative disease: refining the hypothesis
    Mark R Cookson
    Ann Neurol 56:315-6. 2004
  100. ncbi request reprint Biochemical characterization of torsinB
    Casey O'Farrell
    Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Brain Res Mol Brain Res 127:1-9. 2004
    ..These results show that torsins A and B are similar proteins, although there are differences in the abundance of the two homologues and in their recruitment into Lewy bodies...