Research Topics
Genomes and Genes
| Benoit I GiassonSummaryAffiliation: University of Pennsylvania Country: USA Publications
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Detail Information
Publications
Mutations in LRRK2 as a cause of Parkinson's diseaseBenoit I Giasson
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 6084, USA
Neurosignals 16:99-105. 2008....- Mitochondrial injury: a hot spot for parkinsonism and Parkinson's disease?Benoit I Giasson
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Sci Aging Knowledge Environ 2004:pe42. 2004.... - Biochemical and pathological characterization of Lrrk2Benoit I Giasson
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
Ann Neurol 59:315-22. 2006..The studies herein explore the biological and pathological properties of Lrrk2... - Reversible inhibition of alpha-synuclein fibrillization by dopaminochrome-mediated conformational alterationsErin H Norris
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 280:21212-9. 2005..Thus, decreased dopamine levels in substantia nigra neurons might promote alpha-syn aggregation in Parkinson's disease... - Cytosolic catechols inhibit alpha-synuclein aggregation and facilitate the formation of intracellular soluble oligomeric intermediatesJoseph R Mazzulli
The Joseph Stokes Jr Research Institute, The Children s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Neurosci 26:10068-78. 2006..These data indicate that intraneuronal dopamine levels can be a major modulator of alpha-syn aggregation and inclusion formation, with important implications on the selective degeneration of these neurons in Parkinson's disease... - Cleavage of alpha-synuclein by calpain: potential role in degradation of fibrillized and nitrated species of alpha-synucleinAmanda J Mishizen-Eberz
Department of Neurology, University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
Biochemistry 44:7818-29. 2005..These results provide insight into possible disease mechanisms underlying synucleinopathies since the formation of alpha-syn fibrils could be causally linked to the onset/progression of these disorders... 
Clinical and pathological characteristics of patients with leucine-rich repeat kinase-2 mutationsJason P Covy
Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
Mov Disord 24:32-9. 2009..These findings extend the clinical and pathological features that may be associated with LRRK2 mutations...- Mouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degenerationIkuru Yazawa
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Neuron 45:847-59. 2005.... - Convergence of heat shock protein 90 with ubiquitin in filamentous alpha-synuclein inclusions of alpha-synucleinopathiesKunihiro Uryu
The Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104 4283, USA
Am J Pathol 168:947-61. 2006..These data implicate predominantly Hsp90 in the formation of alpha-syn inclusions in PD and related alpha-synucleinopathies... - Specificity and regulation of casein kinase-mediated phosphorylation of alpha-synucleinElisa A Waxman
Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
J Neuropathol Exp Neurol 67:402-16. 2008..These data provide novel explanations for the presence of hyperphosphorylated Ser129 alpha-syn in pathologic inclusions... - Ubiquitination of alpha-synuclein is not required for formation of pathological inclusions in alpha-synucleinopathiesDeepak M Sampathu
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Am J Pathol 163:91-100. 2003..These results suggest that ubiquitination of alpha-synuclein is not required for inclusion formation and follows the fibrillization of alpha-synuclein... - E46K human alpha-synuclein transgenic mice develop Lewy-like and tau pathology associated with age-dependent, detrimental motor impairmentKristel L Emmer
Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 286:35104-18. 2011..Collectively, these findings provide insights in the mechanisms of formation of these aberrant proteinaceous inclusions and support the notion that α-syn aggregates are involved in the pathogenesis of human diseases... - DJ-1 is critical for mitochondrial function and rescues PINK1 loss of functionLing Yang Hao
Department of Biology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 107:9747-52. 2010..These findings link DJ-1, pink1, and parkin to mitochondrial integrity and provide the foundation for therapeutics that link bioenergetics and parkinsonism... - The E46K mutation in alpha-synuclein increases amyloid fibril formationEric A Greenbaum
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 280:7800-7. 2005..These findings support the notion that aberrant alpha-synuclein polymerization resulting in the formation of pathological inclusions can lead to disease... - Leucine-rich repeat kinase 2 expression leads to aggresome formation that is not associated with alpha-synuclein inclusionsElisa A Waxman
Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
J Neuropathol Exp Neurol 68:785-96. 2009..Thus, although LRRK2 is a model system for aggresome formation, LRRK2 is not present in alpha-syn pathological inclusions... - Characterization of hydrophobic residue requirements for alpha-synuclein fibrillizationElisa A Waxman
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Biochemistry 48:9427-36. 2009.... - L10p and P158DEL DJ-1 mutations cause protein instability, aggregation, and dimerization impairmentsChenere P Ramsey
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
J Neurosci Res 88:3111-24. 2010..Taken together, these findings suggest that diverse aberrant mechanisms, including alterations in protein stability and protein folding, are associated with the pathogenicity of the L10P and P158DEL DJ-1 variants... - Identification and characterization of a novel endogenous murine parkin mutationChenere P Ramsey
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
J Neurochem 113:402-17. 2010.... - More than just two peas in a pod: common amyloidogenic properties of tau and alpha-synuclein in neurodegenerative diseasesVirginia M Y Lee
The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and Institute on Aging, The University of Pennsylvania, Philadelphia, PA 19104 4283, USA
Trends Neurosci 27:129-34. 2004..Thus, the ability of tau and alpha-synuclein to affect each other directly or indirectly might contribute to the overlap in the clinical and pathological features of tauopathies and synucleinopathies... - Effects of oxidative and nitrative challenges on alpha-synuclein fibrillogenesis involve distinct mechanisms of protein modificationsErin H Norris
Center for Neurodegenerative Disease Research and the Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 278:27230-40. 2003..These findings demonstrate that nitrative and/or oxidative stress results in distinct mechanisms of alpha-synuclein protein modifications that can influence the formation of stable alpha-synuclein fibrils... - Degradative organelles containing mislocalized alpha-and beta-synuclein proliferate in presenilin-1 null neuronsChristina A Wilson
Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA 19104, USA
J Cell Biol 165:335-46. 2004.... - Pesticide exposure exacerbates alpha-synucleinopathy in an A53T transgenic mouse modelErin H Norris
Center for Neurodegenerative Disease Research, Institute on Aging, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3600 Spruce St, Maloney 3, HUP, Philadelphia, PA 19104 4283, USA
Am J Pathol 170:658-66. 2007..These studies support the notion that environmental factors causing nitrative damage are closely linked to mechanisms underlying the formation of alpha-synuclein pathologies and the onset of Parkinson's-like neurodegeneration... - DJ-1 deficient mice demonstrate similar vulnerability to pathogenic Ala53Thr human alpha-syn toxicityChenere P Ramsey
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
Hum Mol Genet 19:1425-37. 2010..It is possible that alpha-syn and DJ-1 mutations may lead to PD via independent mechanisms... - The E163K DJ-1 mutant shows specific antioxidant deficiencyChenere P Ramsey
Department of Pharmacology, University of Pennsylvania School of Medicine, 125 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, USA
Brain Res 1239:1-11. 2008..These findings suggest that DJ-1 influences several neuroprotective pathways and that the E163K mutation impairs the mechanism that is more specific to oxidative stress... - Fibrillization of alpha-synuclein and tau in familial Parkinson's disease caused by the A53T alpha-synuclein mutationPaul T Kotzbauer
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Exp Neurol 187:279-88. 2004..Our data implicate fibrillization of alpha-syn and tau in the pathogenesis of PD, and suggest that distinct amyloidogenic proteins may cross-seed each other in neurodegenerative diseases... - The G2019S pathogenic mutation disrupts sensitivity of leucine-rich repeat kinase 2 to manganese kinase inhibitionJason P Covy
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6084, USA
J Neurochem 115:36-46. 2010..From these findings, a new model is proposed for a possible function of LRRK2 and the consequence of the G2019S LRRK2 pathogenic mutation... - Tau and 14-3-3 in glial cytoplasmic inclusions of multiple system atrophyBenoit I Giasson
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3rd Floor Maloney Building, Philadelphia, PA 19104, USA
Acta Neuropathol 106:243-50. 2003.... - Role of alpha-synuclein carboxy-terminus on fibril formation in vitroIan V J Murray
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Biochemistry 42:8530-40. 2003..Thus, the carboxy-terminus of alpha-syn may regulate aggregation of full-length alpha-syn and determine the diameter of alpha-syn filaments... - Distinct cleavage patterns of normal and pathologic forms of alpha-synuclein by calpain I in vitroAmanda J Mishizen-Eberz
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
J Neurochem 86:836-47. 2003..Elucidating the role of calpain I in the proteolytic processing of alpha-syn in normal and diseased brains may clarify mechanisms of neurodegenerative alpha-synucleinopathies... - Novel monoclonal antibodies demonstrate biochemical variation of brain parkin with ageAaron C Pawlyk
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 278:48120-8. 2003.... - Nitration of tau protein is linked to neurodegeneration in tauopathiesTakashi Horiguchi
Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 4283, USA
Am J Pathol 163:1021-31. 2003..Taken together, these findings imply that nitrative injury is directly linked to the formation of filamentous tau inclusions... - A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114Adam S Crystal
The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
J Neurochem 86:1359-68. 2003.... - Role of oxidative damage in protein aggregation associated with Parkinson's disease and related disordersErin H Norris
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Antioxid Redox Signal 7:672-84. 2005..Differences in the level, type, and temporal sequence of the oxidative alterations appear to result in both inhibitory and stimulatory effects on the fibrillogenesis of these proteins... - Interactions of amyloidogenic proteinsBenoit I Giasson
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-4283, USA
Neuromolecular Med 4:49-58. 2003..These results indicate that the formation of amyloid composed of different proteins can affect each other directly or indirectly, likely contributing to the overlap in clinical and pathological features... - A novel, high-efficiency cellular model of fibrillar alpha-synuclein inclusions and the examination of mutations that inhibit amyloid formationElisa A Waxman
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 6084, USA
J Neurochem 113:374-88. 2010..This novel high-efficiency cellular model of alpha-syn aggregation is a valuable system that may be used to further understand alpha-syn aggregation and allow for the generation of future therapeutics... - Characterization of antibodies that selectively detect alpha-synuclein in pathological inclusionsElisa A Waxman
Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, 123 John Morgan Building, Philadelphia, PA, 19104, USA
Acta Neuropathol 116:37-46. 2008.... - Alpha-synuclein: normal function and role in neurodegenerative diseasesErin H Norris
Center for Neurodegenerative Disease Research and the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Curr Top Dev Biol 60:17-54. 2004..Therefore, research must be continued in order to better understand the functions of the synuclein proteins under normal physiological conditions as well as their role in diseases... - α-Synuclein, leucine-rich repeat kinase-2, and manganese in the pathogenesis of Parkinson diseaseJason P Covy
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
Neurotoxicology 32:622-9. 2011.... - Studies of protein aggregation in A53T α-synuclein transgenic, Tg2576 transgenic, and P246L presenilin-1 knock-in cross bred miceKristel L Emmer
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 6084, USA
Neurosci Lett 507:137-42. 2012..These studies show that Aβ amyloid deposits can cause the local aggregation of α-syn, but these did not lead to more extensive α-syn pathology... - Are ubiquitination pathways central to Parkinson's disease?Benoit I Giasson
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Cell 114:1-8. 2003.... - Induction of intracellular tau aggregation is promoted by α-synuclein seeds and provides novel insights into the hyperphosphorylation of tauElisa A Waxman
Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
J Neurosci 31:7604-18. 2011..The current work not only provides an exceptional cellular model of tau pathology, but also examines α-syn-induced tau inclusion formation and provides novel insights into hyperphosphorylation observed in disease... - Novel antibodies to synuclein show abundant striatal pathology in Lewy body diseasesJohn E Duda
Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
Ann Neurol 52:205-10. 2002.... - Residue Glu83 plays a major role in negatively regulating alpha-synuclein amyloid formationElisa A Waxman
Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, 125 John Morgan Building, Philadelphia, PA 19104 6084, USA
Biochem Biophys Res Commun 391:1415-20. 2010.... 
Characterization of kinases involved in the phosphorylation of aggregated α-synucleinElisa A Waxman
Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
J Neurosci Res 89:231-47. 2011....- Identification of compounds that inhibit the kinase activity of leucine-rich repeat kinase 2Jason P Covy
Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, 125 John Morgan Building, Philadelphia, PA 19104 6084, USA
Biochem Biophys Res Commun 378:473-7. 2009..These findings provide important insights and tools to study the mechanisms of LRRK2 pathobiology, and could lead to therapeutic applications... - Snaring the function of alpha-synucleinNancy M Bonini
Department of Biology and Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Cell 123:359-61. 2005..These proteins are crucial for release of neurotransmitters at the neuronal synapse, vesicle recycling, and synaptic integrity... - Molecular mechanisms of alpha-synuclein neurodegenerationElisa A Waxman
Department of Pharmacology, University of Pennsylvania School of Medicine, 125 John Morgan Building, Philadelphia, PA 19104 6084, USA
Biochim Biophys Acta 1792:616-24. 2009..In this review, some of the evidence for the different mechanisms of alpha-synuclein toxicity is presented and discussed... - Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synucleinBenoit I Giasson
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, 3600 Spruce Street, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
Neuron 34:521-33. 2002..These mice demonstrate that A53T alpha-synuclein leads to the formation of toxic filamentous alpha-synuclein neuronal inclusions that cause neurodegeneration... - Gamma-synuclein promotes cancer cell survival and inhibits stress- and chemotherapy drug-induced apoptosis by modulating MAPK pathwaysZhong Zong Pan
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
J Biol Chem 277:35050-60. 2002.... - Role of mitochondrial dysfunction in Parkinson's disease: Implications for treatmentChenere P Ramsey
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6084, USA
Drugs Aging 24:95-105. 2007.... - The environmental toxin arsenite induces tau hyperphosphorylationBenoit I Giasson
University of Pennsylvania School of Medicine, Third Floor Maloney Building, 3600 Spruce Street, Philadelphia, Pennsylvania 19104, USA
Biochemistry 41:15376-87. 2002.... - The relationship between oxidative/nitrative stress and pathological inclusions in Alzheimer's and Parkinson's diseasesBenoit I Giasson
Center for Neurodegenerative Disease Research and Department of Pathology and Laboratory Medicine, The University of Pennsylvania, Philadelphia, PA 19104-4283, USA
Free Radic Biol Med 32:1264-75. 2002..It can be surmised that oxidative/nitrative stress, which is cooperatively influenced by environmental factors, genetic predisposition, and senescence, may be a link between these disorders... - DJ-1 is present in a large molecular complex in human brain tissue and interacts with alpha-synucleinMarc C Meulener
Department of Biology and Laboratory of Medicine of University of Pennsylvania, Philadelphia 19104 6084, USA
J Neurochem 93:1524-32. 2005..Furthermore, our results provide further evidence for the interplay between neurodegenerative disease-associated proteins... - Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindredJohn E Duda
Parkinson s Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Pennsylvania, USA
Acta Neuropathol 104:7-11. 2002..We suggest that it is important to recognize that the neurodegenerative process caused by the Ala53Thr mutation in alpha-synuclein is not identical to that seen in typical idiopathic Parkinson's disease brains... - Initiation and synergistic fibrillization of tau and alpha-synucleinBenoit I Giasson
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine
Science 300:636-40. 2003..This suggests that interactions between alpha-syn and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases... - Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathiesManuela Neumann
Department of Neuropathology, Ludwig Maximilians University, Munich, Germany
J Clin Invest 110:1429-39. 2002..The transgenic mice showed a progressive deterioration of locomotor function. Thus, misfolding and hyperphosphorylation of alphaS may cause dysfunction of affected brain regions... - Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cellsAndis Klegeris
Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada
FASEB J 20:2000-8. 2006..5 microM respectively. We hypothesize that the neuroinflammation stimulated by release of an excess of normal alpha-synuclein or by release of its mutated forms can be involved in the pathobiology of PD... - Functional consequences of alpha-synuclein tyrosine nitration: diminished binding to lipid vesicles and increased fibril formationRoberto Hodara
Stokes Research Institute and Department of Biochemistry and Biophysics, Children s Hospital of Philadelphia and The University of Pennsylvania, 19104, USA
J Biol Chem 279:47746-53. 2004..Collectively, these data suggest that post-translational modification of alpha-syn by nitration can promote the formation of intracytoplasmic inclusions that constitute the hallmark of Parkinson disease and other synucleinopathies... - A precipitating role for truncated alpha-synuclein and the proteasome in alpha-synuclein aggregation: implications for pathogenesis of Parkinson diseaseChang wei Liu
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 75390, USA
J Biol Chem 280:22670-8. 2005..This model has parallels in other neurodegenerative diseases, such as Huntington disease, where coaggregation of poly(Q) fragments with full-length protein has been observed...