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Updated: May 28, 2026
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Reagents that block neuronal death from Huntington's disease also curb oxidative stress
Antonio Valencia1, Ellen Sapp, Patrick B Reeves
1Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
Abstract:
Patients with Huntington's disease suffer severe neuronal loss and signs of oxidative damage in the brain. Previously we found that primary neurons from embryonic cortex of mice bearing the Huntington's disease mutation (140 glutamines inserted into exon 1 of huntingtin) showed higher levels of reactive oxygen species before cell death. Here, we treated mutant neurons with known neuroprotective agents and determined the effects on neuronal survival and levels of reactive oxygen species. Primary neurons were exposed to the neurotrophin, brain derived neurotrophic factor, the antioxidant N-acetyl-cysteine or a specific inhibitor of glycogen synthase kinase 3-β, SB216763. Each reagent increased the survival of the mutant neurons compared with untreated mutant neurons and also reduced the levels of reactive oxygen species to levels of wild-type neurons. These results suggest that reducing the levels of reactive oxygen species may be necessary to protect neurons with the Huntington's disease mutation from cell death.
Insights
Neuroprotective agents reduced reactive oxygen species and improved neuronal survival in Huntington's disease models. Targeting oxidative stress is crucial for protecting neurons affected by this genetic mutation.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Huntington's disease (HD) is characterized by significant neuronal loss and oxidative damage in the brain.
- Previous research indicated elevated reactive oxygen species (ROS) in neurons with the HD mutation before cell death.
Purpose of the Study:
- To investigate the neuroprotective effects of specific agents on neurons with the HD mutation.
- To determine the impact of these agents on neuronal survival and ROS levels.
Main Methods:
- Primary neurons from mice with the HD mutation were treated with brain-derived neurotrophic factor (BDNF), N-acetylcysteine (NAC), or SB216763 (a GSK-3β inhibitor).
- Neuronal survival rates and intracellular ROS levels were measured and compared to untreated mutant neurons and wild-type neurons.
Main Results:
- All tested neuroprotective agents significantly increased the survival of mutant neurons.
- Treatment with BDNF, NAC, or SB216763 reduced ROS levels in mutant neurons to those observed in wild-type neurons.
Conclusions:
- Reducing oxidative stress through agents like BDNF, NAC, or SB216763 shows promise for protecting neurons in Huntington's disease.
- Lowering ROS levels may be a necessary therapeutic strategy for combating neuronal cell death in HD.
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