Levodopa drug induced alteration of thiol homeostasis in model neurons activates apoptosis signaling kinase 1: Implications for the treatment of Parkinson's disease
Year: 2010
Type: article
Abstract: ELIZABETH ANN SABENSParkinson's disease (PD), the second most common neurodegenerative disease, is characterized by dopaminergic neuron loss, increased oxidative stress, mitochondrial dysfunction, and protein aggregation.Treatment of PD involves chronic administration of Levodopa (L-DOPA) which paradoxically induces cell death in cellular models of PD.We hypothesized that L-DOPA-induced cell death occurs due to increased oxidative stress disrupting sulfhydryl homeostasis through modification of homeostatic enzymes, glutaredoxin (Grx), GSSG reductase (GR), thioredoxin (Trx), and thioredoxin reductase (TR).Indeed, L-DOPA inhibited Grx in a dose-dependent fashion; however, its content was unaffected.GR activity was not altered.L-DOPA treatments also led to decreased activities of Trx and TR, usually concomitant with diminution of their cellular levels.Experiments involving treatment of the isolated enzymes with oxidized L-DOPA
Author: Elizabeth A. Sabens
Institution: Case Western Reserve University
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2304664544