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Full-Text Articles in Medicine and Health Sciences
The Herbicide Paraquat Causes Up-Regulation And Aggregation Of Α-Synuclein In Mice: Paraquat And Α-Synuclein, Amy B. Manning-Bog, Alison L. Mccormack, Jie Li, Vladimir N. Uversky, Anthony L. Fink, Donato A. Di Monte
The Herbicide Paraquat Causes Up-Regulation And Aggregation Of Α-Synuclein In Mice: Paraquat And Α-Synuclein, Amy B. Manning-Bog, Alison L. Mccormack, Jie Li, Vladimir N. Uversky, Anthony L. Fink, Donato A. Di Monte
Molecular Medicine Faculty Publications
α-Synuclein-containing aggregates represent a feature of a variety of neurodegenerative disorders, including Parkinson's disease (PD). However, mechanisms that promote intraneuronal α-synuclein assembly remain poorly understood. Because pesticides, particularly the herbicide paraquat, have been suggested to play a role as PD risk factors, the hypothesis that interactions between α-synuclein and these environmental agents may contribute to aggregate formation was tested in this study. Paraquat markedly accelerated the in vitro rate of α-synuclein fibril formation in a dose-dependent fashion. When mice were exposed to the herbicide, brain levels of α-synuclein were significantly increased. This up-regulation followed a consistent pattern, with higher α-synuclein …
Elucidation Of The Molecular Mechanism During The Early Events In Immunoglobulin Light Chain Amyloid Fibrillation: Evidence For An Off-Pathway Oligomer At Acidic Ph, Pierre O. Souillac, Vladimir N. Uversky, Ian S. Millett, Ritu Khurana, Sebastian Doniach, Anthony L. Fink
Elucidation Of The Molecular Mechanism During The Early Events In Immunoglobulin Light Chain Amyloid Fibrillation: Evidence For An Off-Pathway Oligomer At Acidic Ph, Pierre O. Souillac, Vladimir N. Uversky, Ian S. Millett, Ritu Khurana, Sebastian Doniach, Anthony L. Fink
Molecular Medicine Faculty Publications
Light chain amyloidosis involves the systemic pathologic deposition of monoclonal light chain variable domains of immunoglobulins as insoluble fibrils. The variable domain LEN was obtained from a patient who had no overt amyloidosis; however, LEN forms fibrils in vitro, under mildly destabilizing conditions. The in vitro kinetics of fibrillation were investigated using a wide variety of probes. The rate of fibril formation was highly dependent on the initial protein concentration. In contrast to most amyloid systems, the kinetics became slower with increasing LEN concentrations. At high protein concentrations a significant lag in time was observed between the conformational changes …
Biophysical Properties Of The Synucleins And Their Propensities To Fibrillate: Inhibition Of Α-Synuclein Assembly By Β- And Γ-Synucleins, Vladimir N. Uversky, Jie Li, Pierre O. Souillac, Ian S. Millett, Sebastian Doniach, Ross Jakes, Michael Goedert, Anthony L. Fink
Biophysical Properties Of The Synucleins And Their Propensities To Fibrillate: Inhibition Of Α-Synuclein Assembly By Β- And Γ-Synucleins, Vladimir N. Uversky, Jie Li, Pierre O. Souillac, Ian S. Millett, Sebastian Doniach, Ross Jakes, Michael Goedert, Anthony L. Fink
Molecular Medicine Faculty Publications
The pathological hallmark of Parkinson's disease is the presence of intracellular inclusions, Lewy bodies, and Lewy neurites, in the dopaminergic neurons of the substantia nigra and several other brain regions. Filamentous α-synuclein is the major component of these deposits and its aggregation is believed to play an important role in Parkinson's disease and several other neurodegenerative diseases. Two homologous proteins, β- and γ-synucleins, are also abundant in the brain. The synucleins are natively unfolded proteins. β-Synuclein, which lacks 11 central hydrophobic residues compared with its homologs, exhibited the properties of a random coil, whereas α- and γ-synucleins were slightly more …