David K Simon

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Do somatic mitochondrial DNA mutations contribute to Parkinson's disease?
    Joanne Clark
    Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, E CLS 628, Boston, MA 02215, USA
    Parkinsons Dis 2011:659694. 2011
  2. pmc Oral N-acetyl-cysteine attenuates loss of dopaminergic terminals in alpha-synuclein overexpressing mice
    Joanne Clark
    Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America
    PLoS ONE 5:e12333. 2010
  3. pmc Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease
    David K Simon
    Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
    BMC Med Genet 11:53. 2010
  4. ncbi Mitochondrial complex I gene variant associated with early age at onset in spinocerebellar ataxia type 2
    David K Simon
    Department of Neurology, Beth Israel Deaconess Medical Center, 77 Avenue Louis Pasteur, Room HIM 847, Boston, MA 02115, USA
    Arch Neurol 64:1042-4. 2007
  5. ncbi Mistaken diagnosis of psychogenic gait disorder in a man with status cataplecticus ("limp man syndrome")
    David K Simon
    Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Boston, Massachusetts 02115, USA
    Mov Disord 19:838-40. 2004
  6. pmc Caffeine and progression of Parkinson disease
    David K Simon
    Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
    Clin Neuropharmacol 31:189-96. 2008
  7. ncbi A heteroplasmic mitochondrial complex I gene mutation in adult-onset dystonia
    David K Simon
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA
    Neurogenetics 4:199-205. 2003
  8. pmc Pgc-1α overexpression downregulates Pitx3 and increases susceptibility to MPTP toxicity associated with decreased Bdnf
    Joanne Clark
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    PLoS ONE 7:e48925. 2012
  9. pmc The c.-237_236GA>TT THAP1 sequence variant does not increase risk for primary dystonia
    Jianfeng Xiao
    Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    Mov Disord 26:549-52. 2011
  10. ncbi Somatic mitochondrial DNA mutations in single neurons and glia
    Ippolita Cantuti-Castelvetri
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
    Neurobiol Aging 26:1343-55. 2005

Detail Information

Publications33

  1. pmc Do somatic mitochondrial DNA mutations contribute to Parkinson's disease?
    Joanne Clark
    Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, E CLS 628, Boston, MA 02215, USA
    Parkinsons Dis 2011:659694. 2011
    ..Together these data support, but do not yet prove, the hypothesis that the accumulation of somatic mtDNA mutations in SN neurons contribute to the pathogenesis of PD...
  2. pmc Oral N-acetyl-cysteine attenuates loss of dopaminergic terminals in alpha-synuclein overexpressing mice
    Joanne Clark
    Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America
    PLoS ONE 5:e12333. 2010
    ..Overall, these results indicate that oral NAC supplementation decreases SNCA levels in brain and partially protects against loss of dopaminergic terminals associated with overexpression of alpha-synuclein in this model...
  3. pmc Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease
    David K Simon
    Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
    BMC Med Genet 11:53. 2010
    ..We investigated the potential contribution of mtDNA variants or mutations to the risk of PD...
  4. ncbi Mitochondrial complex I gene variant associated with early age at onset in spinocerebellar ataxia type 2
    David K Simon
    Department of Neurology, Beth Israel Deaconess Medical Center, 77 Avenue Louis Pasteur, Room HIM 847, Boston, MA 02115, USA
    Arch Neurol 64:1042-4. 2007
    ..We hypothesized that this variant might have a protective effect on the central nervous system and therefore might delay the onset of symptoms in spinocerebellar ataxia type 2 (SCA2)...
  5. ncbi Mistaken diagnosis of psychogenic gait disorder in a man with status cataplecticus ("limp man syndrome")
    David K Simon
    Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Boston, Massachusetts 02115, USA
    Mov Disord 19:838-40. 2004
    ..The gait difficulties resolved with venlafaxine. This case demonstrates that status cataplecticus can be misdiagnosed as a psychogenic gait disorder...
  6. pmc Caffeine and progression of Parkinson disease
    David K Simon
    Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
    Clin Neuropharmacol 31:189-96. 2008
    ..We assessed this relationship using data from 2 recent clinical trials of PD...
  7. ncbi A heteroplasmic mitochondrial complex I gene mutation in adult-onset dystonia
    David K Simon
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA
    Neurogenetics 4:199-205. 2003
    ..01). This difference remains significant even after excluding the index patient (P=0.04). These data suggest that, among haplogroup H subjects, the presence of the A3796G mutation increases the risk of developing adult-onset dystonia...
  8. pmc Pgc-1α overexpression downregulates Pitx3 and increases susceptibility to MPTP toxicity associated with decreased Bdnf
    Joanne Clark
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    PLoS ONE 7:e48925. 2012
    ..These data may have ramifications for neuroprotective strategies targeting overexpression of PGC-1α in PD...
  9. pmc The c.-237_236GA>TT THAP1 sequence variant does not increase risk for primary dystonia
    Jianfeng Xiao
    Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    Mov Disord 26:549-52. 2011
    ..Sequence variants in coding and noncoding regions of THAP1 have been associated with primary dystonia...
  10. ncbi Somatic mitochondrial DNA mutations in single neurons and glia
    Ippolita Cantuti-Castelvetri
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
    Neurobiol Aging 26:1343-55. 2005
    ..These mutations may contribute to changes in brain function during normal aging and neurodegenerative disorders...
  11. pmc Behavioral and metabolic characterization of heterozygous and homozygous POLG mutator mice
    Ying Dai
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Mitochondrion 13:282-91. 2013
    ..These results indicate that high levels of somatic mtDNA mutations can contribute to dopaminergic dysfunction and to behavioral and metabolic deficits...
  12. pmc Association of PGC-1alpha polymorphisms with age of onset and risk of Parkinson's disease
    Joanne Clark
    Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Room CLS 638, Boston, MA 02215, USA
    BMC Med Genet 12:69. 2011
    ..In the current study we analyzed whether rs8192678 or other PGC-1α SNPs affect PD risk or age of onset, singularly or in association with the A10398G SNP...
  13. pmc Mitochondrial DNA deletions in mice in men: substantia nigra is much less affected in the mouse
    Xinhong Guo
    Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
    Biochim Biophys Acta 1797:1159-62. 2010
    ..On a more general note, these results support the view that critical targets of the various aging processes may differ significantly between distant species...
  14. ncbi Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators
    Julie St-Pierre
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 127:397-408. 2006
    ..These studies reveal that PGC-1alpha is a broad and powerful regulator of ROS metabolism, providing a potential target for the therapeutic manipulation of these important endogenous toxins...
  15. ncbi Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson's disease
    David K Simon
    Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
    Neurobiol Aging 25:71-81. 2004
    ..These results indicate that individually rare mtDNA point mutations reach a high aggregate burden in FCtx and SN of elderly subjects...
  16. ncbi A common NURR1 polymorphism associated with Parkinson disease and diffuse Lewy body disease
    Kangni Zheng
    Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
    Arch Neurol 60:722-5. 2003
    ..NURR1 plays a key role in mesencephalic dopaminergic neuron development and survival. A homozygous NURR1 polymorphism (a single base-pair insertion in intron 6) (NI6P) has been reported to be associated with Parkinson disease (PD)...
  17. pmc Rapamycin drives selection against a pathogenic heteroplasmic mitochondrial DNA mutation
    Ying Dai
    Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Hum Mol Genet 23:637-47. 2014
    ....
  18. ncbi Spongiform encephalopathy mimicking corticobasal degeneration
    David J Anschel
    Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Mov Disord 17:606-7. 2002
    ..The following case of SSE presented clinically similar to corticobasal degeneration. The SSE diagnosis was suspected because of magnetic resonance imaging (MRI) findings and confirmed pathologically...
  19. pmc Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival
    Junghee Lee
    Neurology Department, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 280:40398-401. 2005
    ....
  20. doi Transcribe to survive: transcriptional control of antioxidant defense programs for neuroprotection in Parkinson's disease
    Joanne Clark
    Beth Israel Deaconess Medical Center, Department of Neurology, Boston, Massachusetts 02215, USA
    Antioxid Redox Signal 11:509-28. 2009
    ..This review will explore the mechanisms behind the induction of NRF2 and PGC-1alpha in response to oxidative stress and identify common pathways that may provide targets for upregulating antioxidant defense programs...
  21. pmc High-throughput mutational analysis of TOR1A in primary dystonia
    Jianfeng Xiao
    Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA
    BMC Med Genet 10:24. 2009
    ..The aim of this study was to identify TOR1A Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia...
  22. doi Singing in groups for Parkinson's disease (SING-PD): a pilot study of group singing therapy for PD-related voice/speech disorders
    Ludy C Shih
    Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Parkinsonism Relat Disord 18:548-52. 2012
    ..This study suggests that a group singing therapy intervention at this intensity and frequency does not result in significant improvement in objective and subject-rated measures of voice and speech impairment...
  23. pmc Association of cumulative lead exposure with Parkinson's disease
    Marc G Weisskopf
    Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02215, USA
    Environ Health Perspect 118:1609-13. 2010
    ....
  24. pmc Noninvasive brain stimulation for Parkinson's disease and dystonia
    Allan D Wu
    Department of Neurology, University of California, Los Angeles, California 90095, USA
    Neurotherapeutics 5:345-61. 2008
    ..Nonetheless, the noninvasive nature, minimal side effects, positive effects in preliminary clinical studies, and increasing evidence for rational mechanisms make rTMS and tDCS attractive for ongoing investigation...
  25. ncbi Dystonia
    Daniel Tarsy
    Department of Neurology, Parkinson s Disease and Movement Disorders Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA
    N Engl J Med 355:818-29. 2006
  26. pmc Do mtDNA deletions drive premature aging in mtDNA mutator mice?
    Yevgenya Kraytsberg
    Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, United States
    Aging Cell 8:502-6. 2009
    ....
  27. pmc Computationally simple estimation and improved efficiency for special cases of double truncation
    Matthew D Austin
    Department of Biostatistics, Harvard School of Public Health, Boston, MA, 02115, USA
    Lifetime Data Anal 20:335-54. 2014
    ..We demonstrate the consistency and potentially improved efficiency of the estimators in simulation studies, and illustrate their use in application to studies of AIDS incubation and Parkinson's disease age of onset. ..
  28. ncbi Evaluation of the role of Nurr1 in a large sample of familial Parkinson's disease
    William C Nichols
    Division of Human Genetics, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    Mov Disord 19:649-55. 2004
    ..Taken together, these data suggest that genetic alteration at the Nurr1 locus is not a significant risk factor for the development of Parkinson's disease in our large sample of familial PD patients...
  29. ncbi High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain
    Michael T Lin
    Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA
    Hum Mol Genet 11:133-45. 2002
    ..Cytochrome oxidase activity correlated negatively with increasing mutational burden. These findings significantly bolster the mitochondrial theory of aging...
  30. ncbi Rapid and reliable detection of exon rearrangements in various movement disorders genes by multiplex ligation-dependent probe amplification
    Ana Djarmati
    Department of Neurology, University of Lubeck, Lubeck, Germany
    Mov Disord 22:1708-14. 2007
    ....
  31. ncbi No evidence for heritability of Parkinson disease in Swedish twins
    Michael T Lin
    Neurology 64:932; author reply 932. 2005
  32. ncbi Attenuation of free radical production and paracrystalline inclusions by creatine supplementation in a patient with a novel cytochrome b mutation
    Mark A Tarnopolsky
    Department of Medicine, McMaster University Medical Center, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada
    Muscle Nerve 29:537-47. 2004
    ..The results suggest that the development of exercise-induced paracrystalline inclusions may be influenced by the G15497A mtDNA mutation, and that CM mitigates against the pathological consequences of this mutation...

Research Grants10

  1. Parkinson Disease Neuroprotection Clinical Trial
    David Simon; Fiscal Year: 2002
    ..The clinical trial now being planned provides a unique opportunity to determine if similar strategies can yield clinically meaningful neuroprotection in PD. ..
  2. Oxidative Stress, alpha-Synuclein, and mtDNA Mutations in Parkinson's Disease
    David Simon; Fiscal Year: 2009
    ..The proposed experiments will test the hypothesis that the accumulation of somatic mitochondrial DNA mutations in the brain contributes to the pathogenesis of PD, and may lead to novel strategies to slow the progression of PD. ..
  3. Oxidative Stress, alpha-Synuclein, and mtDNA Mutations in Parkinson's Disease
    David Simon; Fiscal Year: 2007
    ..The proposed experiments will test the hypothesis that the accumulation of somatic mitochondrial DNA mutations in the brain contributes to the pathogenesis of PD, and may lead to novel strategies to slow the progression of PD. ..
  4. Somatic Mitochondrial DNA Mutations in Neurons and Glia
    David Simon; Fiscal Year: 2007
    ....
  5. Parkinson Disease Neuroprotection Clinical Trial
    David Simon; Fiscal Year: 2007
    ..The clinical trial now being planned provides a unique opportunity to determine if similar strategies can yield clinically meaningful neuroprotection in PD. ..
  6. Parkinson Disease Neuroprotection Clinical Trial
    David Simon; Fiscal Year: 2006
    ..The clinical trial now being planned provides a unique opportunity to determine if similar strategies can yield clinically meaningful neuroprotection in PD. ..
  7. Acquired Mitochondrial DNA Mutations in the Brain
    David Simon; Fiscal Year: 2006
    ..These studies will lay the foundation for future studies addressing the role of acquired mtDNA mutations in aging and in neurodegenerative diseases. ..
  8. Oxidative Stress, alpha-Synuclein, and mtDNA Mutations in Parkinson's Disease
    David K Simon; Fiscal Year: 2010
    ..The proposed experiments will test the hypothesis that the accumulation of somatic mitochondrial DNA mutations in the brain contributes to the pathogenesis of PD, and may lead to novel strategies to slow the progression of PD. ..