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Genomes and Genes | M Flint BealSummaryAffiliation: Cornell University Country: USA Publications
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Publications
Mitochondrial dysfunction in neurodegenerative diseasesAshu Johri
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA
J Pharmacol Exp Ther 342:619-30. 2012..Here, we provide a concise overview of the major findings in recent years highlighting the importance of healthy mitochondria for a healthy neuron...- Conditional transgenic mice expressing C-terminally truncated human alpha-synuclein (alphaSyn119) exhibit reduced striatal dopamine without loss of nigrostriatal pathway dopaminergic neuronsJoão Paulo L Daher
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, USA
Mol Neurodegener 4:34. 2009..abstract:.. - Neuroprotective effects of compounds with antioxidant and anti-inflammatory properties in a Drosophila model of Parkinson's diseaseKatharina Faust
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
BMC Neurosci 10:109. 2009.... 
Neuroprotective effects of creatineM Flint Beal
Department of Neurology and Neuroscience, Weill Cornell Medical College, 525 East 68th Street, New York, NY 10065, USA
Amino Acids 40:1305-13. 2011..Creatine is now being studied in a phase III clinical trial in HD, the CREST trial. Creatine, therefore, shows great promise in the treatment of a variety of neurodegenerative diseases...
Effects of Coenzyme Q10 in Huntington's disease and early Parkinson's diseaseM Flint Beal
Department of Neurology and Neuroscience, New York Presbyterian Hospital, New York, NY 10021, USA
Biofactors 18:153-61. 2003- The urokinase system of plasminogen activator plays a role in amyotrophic lateral sclerosis (ALS) pathogenesisM Flint Beal
Cornell University Medical College, Department of Neurology, 525 East 68th Street, New York, NY 10021, USA
Exp Neurol 211:332-3. 2008 - Experimental therapeutics in transgenic mouse models of Huntington's diseaseM Flint Beal
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, Room F610, 525 East 68th Street, New York, NY 10021, USA
Nat Rev Neurosci 5:373-84. 2004 - Mitochondria take center stage in aging and neurodegenerationM Flint Beal
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY 10021, USA
Ann Neurol 58:495-505. 2005..Therapeutic approaches targeting mitochondrial dysfunction and oxidative damage in these diseases therefore have great promise... - Mitochondria, oxidative damage, and inflammation in Parkinson's diseaseM Flint Beal
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, USA
Ann N Y Acad Sci 991:120-31. 2003..Of these, coenzyme Q(10) appears to be particularly promising based on the results of a recent phase 2 clinical trial in which it significantly slowed the progression of PD... - Mitochondrial dysfunction and oxidative damage in Alzheimer's and Parkinson's diseases and coenzyme Q10 as a potential treatmentM Flint Beal
Department of Neurology and Neuroscience, New York Presbyterian Hospital Weill Medical College of Cornell University, 525 East 68th Street, New York, New York 10021, USA
J Bioenerg Biomembr 36:381-6. 2004..Lastly, I reviewed the potential efficacy of coenzyme Q as well as a number of other antioxidants in the treatment of both Parkinson's and Alzheimer's diseases... - Mice deficient in dihydrolipoamide dehydrogenase show increased vulnerability to MPTP, malonate and 3-nitropropionic acid neurotoxicityPeter Klivenyi
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York 10021, USA
J Neurochem 88:1352-60. 2004..KGDHC activity was also found to be reduced in putamen from patients with HD. These findings provide further evidence that mitochondrial defects may contribute to the pathogenesis of neurodegenerative diseases... - Loss of Fas ligand-function improves survival in G93A-transgenic ALS miceSusanne Petri
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY, USA
J Neurol Sci 251:44-9. 2006..These results indicate that motor neuron apoptosis triggered by Fas is relevant in ALS pathogenesis... 
Sensitivity to oxidative stress in DJ-1-deficient dopamine neurons: an ES- derived cell model of primary ParkinsonismCecile Martinat
Department of Pathology, Center for Neurobiology and Behavior, and Taub Institute, Columbia University, New York, New York, USA
PLoS Biol 2:e327. 2004..These data are consistent with a protective role for DJ-1, and demonstrate the utility of genetically modified embryonic stem cell-derived neurons as cellular models of neuronal disorders...- Iron porphyrin treatment extends survival in a transgenic animal model of amyotrophic lateral sclerosisAnnie S Wu
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York 10021, USA
J Neurochem 85:142-50. 2003..These results therefore provide further evidence of oxidative damage in a mouse model of ALS, and suggest that FeTCPP could be beneficial for the treatment of ALS patients... - Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseasesLichuan Yang
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, USA
J Neurochem 109:1427-39. 2009..These findings suggest that combination therapy using CoQ(10) and creatine may be useful in the treatment of neurodegenerative diseases such as Parkinson's disease and HD... - N-iminoethyl-L-lysine improves memory and reduces amyloid pathology in a transgenic mouse model of amyloid depositionMagali Dumont
Weill Cornell Medical College, Department of Neurology and Neuroscience, New York, NY 10065, USA
Neurochem Int 56:345-51. 2010..These findings are consistent with previous reports demonstrating that iNOS inhibition ameliorates AD pathogenesis... - Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor against dopamine depletion in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's diseasePeter Klivenyi
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY 10021, USA
J Mol Neurosci 21:191-8. 2003..These results suggest that a combination of a COX-2 inhibitor with creatine might be a useful neuroprotective strategy for PD... - Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of ParkinsonismCarine Cleren
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, USA
J Neurochem 104:1613-21. 2008..These results provide further evidence that administration of CoQ10 is a promising therapeutic strategy for the treatment of PD... - Matrix metalloproteinase-9 is elevated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in miceStefan Lorenzl
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA
Neuromolecular Med 5:119-32. 2004..These results indicate that MMP-9 is induced after MPTP application in mice and that pharmacologic inhibition of MMPs protects against MPTP neurotoxicity... - Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen speciesAnatoly A Starkov
Department of Neurology and Neuroscience, Weill Medical College, Cornell University, New York, New York 10021, USA
J Neurosci 24:7779-88. 2004..These mitochondria also produced significantly less H(2)O(2) than mitochondria isolated from their littermate wild-type mice. The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria... - Lenalidomide (Revlimid) administration at symptom onset is neuroprotective in a mouse model of amyotrophic lateral sclerosisArie Neymotin
Department of Neurology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY, USA
Exp Neurol 220:191-7. 2009..These data encourage further clinical evaluation of lenalidomide as therapeutic strategy to block or slow disease progression in human ALS patients... - Cell-permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosisSusanne Petri
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA
J Neurochem 98:1141-8. 2006..This further enhances the concept that pharmacological modification of oxidative stress is a therapeutic option for the treatment of ALS... - Impairment of PGC-1alpha expression, neuropathology and hepatic steatosis in a transgenic mouse model of Huntington's disease following chronic energy deprivationRajnish K Chaturvedi
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10065, USA
Hum Mol Genet 19:3190-205. 2010.... - Increased survival and neuroprotective effects of BN82451 in a transgenic mouse model of Huntington's diseasePeter Klivenyi
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York 10021, USA
J Neurochem 86:267-72. 2003..These findings provide evidence that novel anti-oxidants such as BN82451 may be useful for treating HD... - Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's diseaseYanping Li
Department of Neurology and Neurosciences, Weill Medical College of Cornell University, New York, New York, USA
Nat Neurosci 12:826-8. 2009..These mice provide a valid model of Parkinson's disease and are a resource for the investigation of pathogenesis and therapeutics... - 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... - Minocycline enhances MPTP toxicity to dopaminergic neuronsLichuan Yang
Neurochemistry and Neurodegenerative Disease Laboratory, Weill Medical College at Cornell University, New York, New York 10021, USA
J Neurosci Res 74:278-85. 2003..We present evidence suggesting that this effect may be due to inhibition of DA and 1-methyl-4-phenylpridium (MPP+) uptake into striatal vesicles... - Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicityCarine Cleren
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York, USA
J Neurochem 94:995-1004. 2005..Celastrol is therefore a promising neuroprotective agent for the treatment of PD and HD... - Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer's mouse modelSaravanan S Karuppagounder
Department of Neurology and Neurosciences, Weill Medical College of Cornell University, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Neurobiol Aging 30:1587-600. 2009..Thus, the induction of mild impairment of oxidative metabolism, oxidative stress and inflammation induced by TD alters metabolism of APP and/or Abeta and promotes accumulation of plaques independent of neuron loss or neuritic clusters... - Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinasePeter Klivenyi
Department of Neurology and Neuroscience, New York-Presbyterian Hospital, Weill Medical College of Cornell University, New York, NY 10021, USA
Neurobiol Dis 15:610-7. 2004.... - Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington's diseaseGabriella Gardian
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York 10021, USA
J Biol Chem 280:556-63. 2005.... - Mice deficient in dihydrolipoyl succinyl transferase show increased vulnerability to mitochondrial toxinsLichuan Yang
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA
Neurobiol Dis 36:320-30. 2009..These observations support the hypothesis that reductions in KGDHC may impair the adaptability of the brain and contribute to the pathogenesis of neurodegenerative diseases... - Mitochondrial DNA and respiratory chain function in spinal cords of ALS patientsFalk R Wiedemann
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, USA
J Neurochem 80:616-25. 2002.... - 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... - Neuroprotective effects of phenylbutyrate against MPTP neurotoxicityGabriella Gardian
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, 525 East 68th Street, Room F610, New York, NY 10021, USA
Neuromolecular Med 5:235-41. 2004..These findings provide further evidence that administration of phenylbutyrate may be a useful approach for the treatment of neurodegenerative diseases... - The lipophilic metal chelators DP-109 and DP-460 are neuroprotective in a transgenic mouse model of amyotrophic lateral sclerosisSusanne Petri
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York, USA
J Neurochem 102:991-1000. 2007..In line with previous studies using metal chelators in the G93A animal model, our results suggest that these compounds have neuroprotective capacities in ALS... - Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosisPeter Klivenyi
Department of Neurology and Neuroscience, New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, New York 10021, USA
J Neurochem 88:576-82. 2004..These results suggest that combinations of therapies targeting different disease mechanisms may be a useful strategy in the treatment of ALS... - Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer's diseaseMagali Dumont
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York 10065, USA
J Neurochem 109:502-12. 2009..CDDO-MA was provided with chow (800 mg/kg) from 1 to 4 months of age. CDDO-MA significantly improved spatial memory retention and reduced plaque burden, Abeta42 levels, microgliosis, and oxidative stress in Tg19959 mice... - Treatment with a catalytic antioxidant corrects the neurobehavioral defect in ataxia-telangiectasia miceSusan E Browne
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA
Free Radic Biol Med 36:938-42. 2004..We show that treatment with a catalytic antioxidant corrects the neurobehavioral deficit in these mice... - A pivotal role of matrix metalloproteinase-3 activity in dopaminergic neuronal degeneration via microglial activationYoon Seong Kim
Burke Medical Research Institute, and Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 1300 York Ave, New York, NY 10021, USA
FASEB J 21:179-87. 2007..Our results could lead to a novel therapeutic approach to PD... - Creatine and its potential therapeutic value for targeting cellular energy impairment in neurodegenerative diseasesPeter J Adhihetty
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA
Neuromolecular Med 10:275-90. 2008..In summary, current literature suggests that exogenous creatine supplementation is most efficacious as a treatment paradigm in Huntington's and Parkinson's disease but appears to be less effective for ALS and Alzheimer's disease... - Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathologyReisuke H Takahashi
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA
Am J Pathol 161:1869-79. 2002..This accumulation was associated with abnormal synaptic morphology, before beta-amyloid plaque pathology, suggesting that intracellular accumulation of beta-amyloid plays a crucial role in Alzheimer's disease... - Reduction of oxidative stress, amyloid deposition, and memory deficit by manganese superoxide dismutase overexpression in a transgenic mouse model of Alzheimer's diseaseMagali Dumont
Weill Cornell Medical College, Department of Neurology and Neuroscience, 525 E 68th St, New York, NY 10065, USA
FASEB J 23:2459-66. 2009.... - Oxidative stress biomarkers in sporadic ALSHiroshi Mitsumoto
Eleanor and Lou Gehrig MDA ALS Research Center, Columbia University Medical Center, New York, NY 10032, USA
Amyotroph Lateral Scler 9:177-83. 2008..ELISA may be reliable and thus useful in epidemiology studies requiring large numbers of samples to determine the significance of increased oxidative stress markers in SALS. Further studies are required... - Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicityLichuan Yang
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, USA
Antioxid Redox Signal 11:2095-104. 2009..These findings provide strong evidence that these neuroprotective peptides, which target both mitochondrial dysfunction and oxidative damage, are a promising approach for the treatment of PD... - Protection from Alzheimer's-like disease in the mouse by genetic ablation of inducible nitric oxide synthaseCarl Nathan
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA
J Exp Med 202:1163-9. 2005..Thus, iNOS seems to be a major instigator of beta-amyloid deposition and disease progression. Inhibition of iNOS may be a therapeutic option in AD... - PGC-1alpha, a new therapeutic target in Huntington's disease?Jetta K McGill
Department of Neurology, Cornell Medical Center, New York, NY 10021, USA
Cell 127:465-8. 2006.... - Stress-induced mitochondrial depolarization and oxidative damage in PSP cybridsJason W Chirichigno
Department of Neurology and Neuroscience, Room A-503, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA
Brain Res 951:31-5. 2002.... - Commentary on "Alpha-synuclein and mitochondria: a tangled skein"M Flint Beal
Weill Medical College of Cornell University, New York, NY 10021, USA
Exp Neurol 186:109-11. 2004 - Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytesNeeta S Roy
Department of Neurology, Weill Medical College of Cornell University, New York, New York 10021, USA
Nat Med 12:1259-68. 2006..Yet these data also mandate caution in the clinical application of HES cell-derived grafts, given their potential for phenotypic instability and undifferentiated expansion... - Mitochondrial biology and oxidative stress in Parkinson disease pathogenesisClaire Henchcliffe
Department of Neurology and Neuroscience at the Weill Medical College of Cornell University, New York, NY 10021, USA
Nat Clin Pract Neurol 4:600-9. 2008.... - Diffusion tensor imaging in the diagnosis of primary lateral sclerosisAziz M Ulug
Department of Radiology, Weill Medical College of Cornell University, New York, New York 10021, USA
J Magn Reson Imaging 19:34-9. 2004..To evaluate the utility of MR diffusion tensor imaging in diagnosing primary lateral sclerosis (PLS)... - Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic miceMarina Mattiazzi
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA
J Biol Chem 277:29626-33. 2002..Our findings suggest that G93A-mutated hSOD1 in mitochondria may cause mitochondrial defects, which contribute to precipitating the neurodegenerative process in motor neurons... - Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseasesGary E Gibson
Department of Neurology and Neuroscience, Weill Cornell Medical College of Cornell University at Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Biochim Biophys Acta 1802:122-34. 2010..Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic approaches in age-associated neurodegenerative diseases... - Coenzyme Q10 as a possible treatment for neurodegenerative diseasesM Flint Beal
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, NY 10021, USA
Free Radic Res 36:455-60. 2002..CoQ10 is presently being studied as a potential treatment for early PD as well as in combination with remacemide as a potential treatment for HD... - Mitochondrial dihydrolipoyl succinyltransferase deficiency accelerates amyloid pathology and memory deficit in a transgenic mouse model of amyloid depositionMagali Dumont
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA
Free Radic Biol Med 47:1019-27. 2009..Our data suggest that alpha-KGDHC may be involved in AD pathogenesis through increased mitochondrial oxidative stress... - Bioenergetic approaches for neuroprotection in Parkinson's diseaseM Flint Beal
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY, USA
Ann Neurol 53:S39-47; discussion S47-8. 2003..Many other agents show good human tolerability. These agents therefore are promising candidates for further study as neuroprotective agents in PD... - Impaired PGC-1alpha function in muscle in Huntington's diseaseRajnish K Chaturvedi
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY 10065, USA
Hum Mol Genet 18:3048-65. 2009..Furthermore, muscle may provide a readily accessible tissue in which to monitor therapeutic interventions... - The role of NADPH oxidase 1-derived reactive oxygen species in paraquat-mediated dopaminergic cell deathAna Clara Cristóvão
Neurology Neuroscience Department, Weill Medical College of Cornell University, New York, New York, USA
Antioxid Redox Signal 11:2105-18. 2009..Our results suggest that Nox1-generated superoxide is implicated in the oxidative stress elicited by paraquat in DA cells, and it can serve as a novel target for pharmacologic intervention... - Multinuclear magnetic resonance spectroscopy for in vivo assessment of mitochondrial dysfunction in Parkinson's diseaseClaire Henchcliffe
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA
Ann N Y Acad Sci 1147:206-20. 2008.... - Therapeutic effects of coenzyme Q10 in neurodegenerative diseasesM Flint Beal
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA
Methods Enzymol 382:473-87. 2004 - Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosisMahmoud Kiaei
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, 525 East 68th Street, Room A 501, New York, NY 10021, USA
Exp Neurol 191:331-6. 2005..Pioglitazone also reduced iNOS, NFkappa-B, and 3-nitrotyrosine immunoreactivity in the spinal cords of G93A transgenic mice. These results suggest that pioglitazone may have therapeutic potential for human ALS... - Neurotoxicity and behavioral deficits associated with Septin 5 accumulation in dopaminergic neuronsJin H Son
Laboratory of Molecular Neurobiology, The W M Burke Medical Research Institute, White Plains, New York 10605, USA
J Neurochem 94:1040-53. 2005..These data suggest that a threshold level of Septin 5 accumulation is required for DAergic cell loss and that l-DOPA-responsive motor deficits can occur even in the presence of elevated DA... - Promethazine protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicityCarine Cleren
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room A 501, NY 10021, USA
Neurobiol Dis 20:701-8. 2005..The sum of data indicates that PMZ is a strong neuroprotective agent capable of protecting dopaminergic neurons against MPTP toxicity in vivo... - Mice lacking alpha-synuclein are resistant to mitochondrial toxinsPeter Klivenyi
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10021, USA
Neurobiol Dis 21:541-8. 2006..These findings implicate alpha-synuclein as a modulator of oxidative damage, which has been implicated in neuronal death produced by MPTP and other mitochondrial toxins... - Therapeutic approaches to mitochondrial dysfunction in Parkinson's diseaseM Flint Beal
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065 4870, USA
Parkinsonism Relat Disord 15:S189-94. 2009..Lastly, newly identified therapeutic targets include peroxisomal proliferator activated receptor gamma-coactivator (PGC-1alpha) and sirtuins. These pathways provide promise for future therapeutic developments in the treatment of PD... - Beta-amyloid 42 accumulation in the lumbar spinal cord motor neurons of amyotrophic lateral sclerosis patientsNoel Y Calingasan
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, F 610, New York, NY 10021, USA
Neurobiol Dis 19:340-7. 2005..These results suggest that aberrant accumulation of A beta42 in ALS spinal cord motor neurons is associated with oxidative stress, and may play a role in the pathogenesis of neurodegeneration in ALS... - Integrative role of cPLA with COX-2 and the effect of non-steriodal anti-inflammatory drugs in a transgenic mouse model of amyotrophic lateral sclerosisMahmoud Kiaei
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, USA
J Neurochem 93:403-11. 2005..These results suggest that cPLA2 plays an important role in supplying arachidonic acid to the COX-2 driven inflammatory pathway in ALS associated with SOD1 mutations... - Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALSSusan E Browne
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 E 68th Street, A 502, New York, NY 10021, USA
Neurobiol Dis 22:599-610. 2006.... - Apocynin administration does not improve behavioral and neuropathological deficits in a transgenic mouse model of Alzheimer's diseaseMagali Dumont
Weill Cornell Medical College, Department of Neurology and Neuroscience, 525 East 68th Street, New York, NY 10065, USA
Neurosci Lett 492:150-4. 2011..Also, the reduction of NOX-mediated oxidative stress may not be sufficient to prevent AD, since other sources of reactive oxygen species such as mitochondria may be more important... - Mitochondrial dysfunction and amyotrophic lateral sclerosisIsabel Hervias
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, A-505, New York, New York 10021, USA
Muscle Nerve 33:598-608. 2006..If mitochondrial dysfunction is convincingly involved in ALS pathogenesis, either as a primary cause or as contributing factor, it is likely to become a novel target for therapeutic intervention... - Behavioral deficits and progressive neuropathology in progranulin-deficient mice: a mouse model of frontotemporal dementiaFangfang Yin
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA
FASEB J 24:4639-47. 2010..Thus, progranulin deficiency induced FTD-like behavioral and neuropathological deficits. These mice may serve as an important tool for deciphering underlying mechanisms in frontotemporal dementia... - Neural mitochondrial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant miceMaria Damiano
The Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, USA
J Neurochem 96:1349-61. 2006..Thus, mitochondrial dysfunction and Ca2+-mediated excitotoxicity are likely to be interconnected mechanisms that contribute to neuronal degeneration in familial amyotrophic lateral sclerosis... - Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout miceFeng Li
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA
J Neurochem 89:1308-12. 2004..These results indicate that oxidative stress can promote the pathogenesis of AD and further support the feasibility of antioxidant approaches for AD therapy... - Metabolomic profiling to develop blood biomarkers for Parkinson's diseaseMikhail Bogdanov
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, 525 East 68th Street, F610, New York, NY 10021, USA
Brain 131:389-96. 2008..These findings show that metabolomic profiling with LCECA coulometric array has great promise for developing biomarkers for both the diagnosis, as well as monitoring disease progression in PD... - Parkinsonism genes: culprits and cluesAsa Abeliovich
Department of Pathology, Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons 15 403, 630 W 168th St, New York, NY 10032, USA
J Neurochem 99:1062-72. 2006..A series of recent publications suggest novel pathways that may link the FP genes... - Reduced creatine kinase activity in transgenic amyotrophic lateral sclerosis miceSilke Wendt
Institute for Cell Biology, , , Switzerland
Free Radic Biol Med 32:920-6. 2002..Our data provide evidence for oxidative damage to the CK system in ALS, which may contribute to impaired energy metabolism and neurodegeneration... - Therapeutic effects of cystamine in a murine model of Huntington's diseaseAlpaslan Dedeoglu
Geriatric Research Education and Clinical Center, Bedford Veterans Affairs Medical Center, Bedford, Massachusetts 01730, USA
J Neurosci 22:8942-50. 2002..These findings are consistent with the hypothesis that transglutaminase activity may play a role in the pathogenesis of HD, and they identify cystamine as a potential therapeutic strategy for treating HD patients... - Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer diseasePatrizia Mecocci
Institute of Gerontology and Geriatrics, University of Perugia, Via Eugubina 42, 06122 Perugia, Italy
Arch Neurol 59:794-8. 2002..A large body of experimental evidence suggests that in Alzheimer disease (AD) pathogenesis an important role is played by oxidative stress, but there is still a lack of data on in vivo markers of free radical-induced damage... - Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional declineClifford W Shults
Department of Neurosciences, Mail Code 0662, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0662, USA
Arch Neurol 59:1541-50. 2002..Parkinson disease (PD) is a degenerative neurological disorder for which no treatment has been shown to slow the progression... - Expression and activity of antioxidants in the brain in progressive supranuclear palsyIppolita Cantuti-Castelvetri
Neurology Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
Brain Res 930:170-81. 2002..Together, our data argues strongly in favor of the involvement of oxidative stress in the etiology and progression of PSP, and suggests that deficit in SOD or glutathione metabolism are not causative... - Cytochrome C and caspase-9 expression in Huntington's diseaseTamara Kiechle
Geriatric Research Education and Clinical Center, Bedford VA Medical Center, MA 01730, USA
Neuromolecular Med 1:183-95. 2002.... - Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's diseaseRobert J Ferrante
Geriatric Research Education and Clinical Center, Bedford Veterans Administration Medical Center, Bedford, Massachusetts 01730, USA
J Neurosci 22:1592-9. 2002.... - The mitochondrial permeability transition as a target for neuroprotectionBruce S Kristal
Dementia Research Service, Burke Medical Research Institute, 785 Mamaroneck Ave, White Plains, New York 10605, USA
J Bioenerg Biomembr 36:309-12. 2004..g., in stroke) and are modulated by diseases of the central nervous system (e.g., Huntington's). Evidence of neuroprotection seen with compounds such as N -Met-Val cyclosporine also support this possibility... - Age-related microglial activation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration in C57BL/6 miceShuei Sugama
Harold L Dorris Neurological Research Center, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA
Brain Res 964:288-94. 2003..The present study suggests that age-related microglial activation in the SN may be relevant to the higher susceptibility to MPTP neurotoxicity in older mice... - Manganese porphyrin given at symptom onset markedly extends survival of ALS miceJohn P Crow
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Ann Neurol 58:258-65. 2005..These results show that the catalytic antioxidant AEOL 10150 provides a pronounced therapeutic benefit with onset administration and is, therefore, a promising agent for the treatment of ALS... - Effects of CAG repeat length, HTT protein length and protein context on cerebral metabolism measured using magnetic resonance spectroscopy in transgenic mouse models of Huntington's diseaseBruce G Jenkins
MGH NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
J Neurochem 95:553-62. 2005..Our results indicate profound metabolic defects that are strongly affected by CAG repeat length, as well as gene expression levels and protein context... - Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signalingYufeng Yang
Department of Pathology, Stanford University School of Medicine, and Geriatric Research, Education and Clinical Center Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA
Proc Natl Acad Sci U S A 102:13670-5. 2005..Manipulation of PI3K/Akt signaling may therefore offer therapeutic benefits for the treatment of PD... - Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in miceShan Zhu
Neuroapoptosis Laboratory, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Neurosci 24:5909-12. 2004..Prophylactic creatine supplementation, similar to what is recommended for an agent such as aspirin, may be considered for patients in high stroke-risk categories... - Clinically approved heterocyclics act on a mitochondrial target and reduce stroke-induced pathologyIrina G Stavrovskaya
Dementia Research Service, Burke Medical Research Institute, 785 Mamaroneck Ave, White Plains, NY 10605, USA
J Exp Med 200:211-22. 2004.... - Oral uridine pro-drug PN401 is neuroprotective in the R6/2 and N171-82Q mouse models of Huntington's diseaseJoel A Saydoff
Neuroscience Research, Wellstat Therapeutics Corporation, 930 Clopper Road, Gaithersburg, MD 20878, USA
Neurobiol Dis 24:455-65. 2006..These results suggest that PN401 may have beneficial effects in the treatment of neurodegenerative diseases such as HD... - Increased affinity for copper mediated by cysteine 111 in forms of mutant superoxide dismutase 1 linked to amyotrophic lateral sclerosisShohei Watanabe
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
Free Radic Biol Med 42:1534-42. 2007..Aberrant Cu binding at the Cys111 residue may be a significant factor in altering mutant SOD1 behavior and may explain the benefit of controlling Cu access to mutant SOD1 in models of familial ALS... - Sequence analysis of the entire mitochondrial genome in Parkinson's diseaseCristofol Vives-Bauza
Centre d' Investigacions en Bioquimica i Biologia Molecular, Hospital Vall d' Hebron, Barcelona, Spain
Biochem Biophys Res Commun 290:1593-601. 2002..Finally, PD and control subjects did not differ in the total number of all mutations, nor the total number of missense mutations. Thus, mtDNA involvement in PD, if any, is likely to be complex and should be reconsidered carefully... - Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease modelsHaruhisa Inoue
Neuroregeneration Laboratories, Udall Parkinson s Disease Center of Excellence, Harvard Medical School and McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Proc Natl Acad Sci U S A 104:14430-5. 2007.... - Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degenerationAndrew D Strand
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
J Neurosci 27:11758-68. 2007..Based on these findings, we present a testable model of HD pathogenesis that, unlike most models, begins to account for regional specificity in human HD and the absence of such specificity in genetic mouse models of HD... - Uncoupling protein 2 prevents neuronal death including that occurring during seizures: a mechanism for preconditioningSabrina Diano
Department of Obstetrics and Gynecology, Yale Medical School, 333 Cedar Street, New Haven Connecticut 06520, USA
Endocrinology 144:5014-21. 2003.... - Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's diseaseP Hemachandra Reddy
Neurogenetics Laboratory, Neurological Sciences Institute, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA
Trends Mol Med 14:45-53. 2008..Here, we describe recent studies regarding the roles of Abeta and mitochondrial function in AD progression and particularly in synaptic damage and cognitive decline... - Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic miceAlpaslan Dedeoglu
Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachussets 01730, USA
J Neurochem 85:1359-67. 2003..These findings have important therapeutic implications, suggesting that creatine therapy initiated after diagnosis may provide significant clinical benefits to HD patients... - Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's diseaseDeepinder Kaur
Buck Institute for Age Research, Novato, CA 94945, USA
Neuron 37:899-909. 2003.... - Decreased striatal dopamine release underlies increased expression of long-term synaptic potentiation at corticostriatal synapses 24 h after 3-nitropropionic-acid-induced chemical hypoxiaGarnik Akopian
Davis School of Gerontology, University of Southern California, Los Angeles, California 90089, USA
J Neurosci 28:9585-97. 2008..Thus, 3-NP causes significant changes in motor behavior marked by parallel changes in striatal dopamine release and corticostriatal synaptic plasticity... - Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disordersM Christine Rodriguez
Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada
Muscle Nerve 35:235-42. 2007..Future studies with larger sample sizes in relatively homogeneous groups will be required to determine whether such combination therapies influence function and quality of life...
Research Grants
- Effects of Coenzyme Q10 in Parkinson Disease-Phase 3M Beal; Fiscal Year: 2007..We will determine the mean plasma coenzyme Q10 levels at baseline and at visits 1, 8 and 16 months, and determine whether the mean correlates with reduction in worsening of the total UPDRS score. ..
- Bioenergetics in Animal Models of Huntington's DiseaseM Beal; Fiscal Year: 2007..We will, therefore, examine whether a combination of creatine or coenzyme Q with either a HDAC inhibitor or a phosphodiesterase IV inhibitor can exert additive neuroprotective effects. ..
- Antioxidant Approaches to Alzheimer's Disease TherapyM Beal; Fiscal Year: 2007..If we can demonstrate significant effects of CoQ10 and L-NIL, this could lead to rapid development of new therapies for slowing the progression of AD. ..
- Development of New Therapies for Huntington's DiseaseM Beal; Fiscal Year: 2007..We believe that these studies will provide critical pre-clinical data to determine the agents, which have the most promise for use as neuroprotective agents in clinical drug trials in HD patients. ..
- Mitochondrial Dysfunction in Alzheimer's DiseaseM Beal; Fiscal Year: 2004..These studies are designed to help to further elucidate the role of mitochondrial dysfunction and oxidative damage in normal aging and AD. ..
- BIOENERGETICS IN ANIMAL MODELS OF HUNTINGTONSM Beal; Fiscal Year: 2002..They also have the potential of leading to new therapeutic interventions which might be useful in the treatment of HD. ..
- Interactions for Pesticides, mitochondria and genetics in Parkinson's disease.M Flint Beal; Fiscal Year: 2010..The study will enrich and refine our understanding of pesticide-induced cell damage pathways observed in sporadic and familial PD and identify new target(s) for intervention in PD pathogenesis. ..