Genomes and Genes
David K Simon
Affiliation: Harvard University
- A heteroplasmic mitochondrial complex I gene mutation in adult-onset dystoniaDavid 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...
- Maternal inheritance and mitochondrial DNA variants in familial Parkinson's diseaseDavid 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...
- Caffeine and progression of Parkinson diseaseDavid 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...
- Mitochondrial complex I gene variant associated with early age at onset in spinocerebellar ataxia type 2David 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)...
- 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...
- The c.-237_236GA>TT THAP1 sequence variant does not increase risk for primary dystoniaJianfeng 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...
- Somatic mitochondrial DNA mutations in single neurons and gliaIppolita 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...
- Association of PGC-1alpha polymorphisms with age of onset and risk of Parkinson's diseaseJoanne 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...
- Mitochondrial DNA deletions in mice in men: substantia nigra is much less affected in the mouseXinhong 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...
- Pgc-1α overexpression downregulates Pitx3 and increases susceptibility to MPTP toxicity associated with decreased BdnfJoanne 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...
- A common NURR1 polymorphism associated with Parkinson disease and diffuse Lewy body diseaseKangni 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)...
- Oral N-acetyl-cysteine attenuates loss of dopaminergic terminals in alpha-synuclein overexpressing miceJoanne 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...
- Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivatorsJulie 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...
- Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson's diseaseDavid 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...
- Spongiform encephalopathy mimicking corticobasal degenerationDavid 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...
- High-throughput mutational analysis of TOR1A in primary dystoniaJianfeng 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...
- Singing in groups for Parkinson's disease (SING-PD): a pilot study of group singing therapy for PD-related voice/speech disordersLudy 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...
- Noninvasive brain stimulation for Parkinson's disease and dystoniaAllan 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...
- 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....
- Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survivalJunghee Lee
Neurology Department, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 280:40398-401. 2005....
- Association of cumulative lead exposure with Parkinson's diseaseMarc G Weisskopf
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02215, USA
Environ Health Perspect 118:1609-13. 2010....
- DystoniaDaniel 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
- Transcribe to survive: transcriptional control of antioxidant defense programs for neuroprotection in Parkinson's diseaseJoanne 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...
- 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...
- High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brainMichael 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...
- Evaluation of the role of Nurr1 in a large sample of familial Parkinson's diseaseWilliam 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...
- No evidence for heritability of Parkinson disease in Swedish twinsMichael T Lin
Neurology 64:932; author reply 932. 2005
- Attenuation of free radical production and paracrystalline inclusions by creatine supplementation in a patient with a novel cytochrome b mutationMark 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...
- Rapid and reliable detection of exon rearrangements in various movement disorders genes by multiplex ligation-dependent probe amplificationAna Djarmati
Department of Neurology, University of Lubeck, Lubeck, Germany
Mov Disord 22:1708-14. 2007....
- Oxidative Stress, alpha-Synuclein, and mtDNA Mutations in Parkinson's DiseaseDavid 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. ..
- Somatic Mitochondrial DNA Mutations in Neurons and GliaDavid Simon; Fiscal Year: 2007....
- Parkinson Disease Neuroprotection Clinical TrialDavid 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. ..
- Acquired Mitochondrial DNA Mutations in the BrainDavid 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. ..
- Oxidative Stress, alpha-Synuclein, and mtDNA Mutations in Parkinson's DiseaseDavid 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. ..