ABSTRACTObjectiveRedox stress, c-Abl activation, and α-synuclein aggregates each independently co... more ABSTRACTObjectiveRedox stress, c-Abl activation, and α-synuclein aggregates each independently contribute to neurodegeneration in Parkinson’s disease. Interactions between these factors may underlie convergent and feed-forward mechanisms of disease progression.Methodsα-synuclein aggregate formation was induced in neuronal cultures and mouse substantia nigra by exposure to pre-formed human α-synuclein fibrils or by AAV-mediated over-expression of α-synuclein. Aggregate formation, c-Abl activation, redox stress, and neurodegeneration were evaluated by immunohistochemistry and Western blots, and mouse motor function was evaluated using the rota-rod and pole tests. To suppress redox stress, cultures and mice were treated with N-acetyl cysteine, a thiol repletion agent that supports neuronal glutathione metabolism.ResultsIn primary neuron cultures, the formation of α-synuclein aggregates led to redox stress and c-Abl activation. Redox stress alone, in the absence of α-synuclein aggregate...
ABSTRACTObjectiveRedox stress, c-Abl activation, and α-synuclein aggregates each independently co... more ABSTRACTObjectiveRedox stress, c-Abl activation, and α-synuclein aggregates each independently contribute to neurodegeneration in Parkinson’s disease. Interactions between these factors may underlie convergent and feed-forward mechanisms of disease progression.Methodsα-synuclein aggregate formation was induced in neuronal cultures and mouse substantia nigra by exposure to pre-formed human α-synuclein fibrils or by AAV-mediated over-expression of α-synuclein. Aggregate formation, c-Abl activation, redox stress, and neurodegeneration were evaluated by immunohistochemistry and Western blots, and mouse motor function was evaluated using the rota-rod and pole tests. To suppress redox stress, cultures and mice were treated with N-acetyl cysteine, a thiol repletion agent that supports neuronal glutathione metabolism.ResultsIn primary neuron cultures, the formation of α-synuclein aggregates led to redox stress and c-Abl activation. Redox stress alone, in the absence of α-synuclein aggregate...
Uploads