Autosomal recessive juvenile parkinsonism Cys212Tyr mutation in parkin renders lymphocytes susceptible to dopamine- and iron-mediated apoptosis
✍ Scribed by Marlene Jimenez Del Rio; Sonia Moreno; Gloria Garcia-Ospina; Omar Buritica; Carlos S. Uribe; Francisco Lopera; Carlos Velez-Pardo
- Book ID
- 102945011
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 621 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0885-3185
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✦ Synopsis
Abstract
Mutations in parkin are implicated in the pathogenesis of autosomal recessive juvenile parkinsonism (AR‐JP) disease. We show that homozygote Cys212Tyr parkin mutation in AR‐JP patients renders lymphocytes sensitive to dopamine, iron and hydrogen peroxide stimuli. Indeed, dopamine‐induced apoptosis by four alternative mechanisms converging on caspase‐3 activation and apoptotic morphology: (1) NF‐κB‐dependent pathway; mitochondrial dysfunction either by (2) H~2~O~2~ or (3) hydroxyl exposure and (4) increase of unfolded–protein stress. We also demonstrate that 17β‐estradiol and testosterone prevent homozygote lymphocytes from oxidative stressors‐evoked apoptosis. These results may contribute to understanding the relationship between genetic and environmental factors and iron in AR‐JP. © 2003 Movement Disorder Society