Dehydroascorbic acid impairs neurite growth through RIPK1-associated caspase activation

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Axonal and neurite loss are hallmarks of neurodegenerative diseases, exacerbated by oxidative stress.
• Vitamin C (ascorbic acid and dehydroascorbic acid) plays a role in brain antioxidant homeostasis.
• Dehydroascorbic acid accumulation is linked to neuronal dysfunction and cell death via RIPK1 activation.

Purpose of the Study:

• To investigate whether dehydroascorbic acid (DHA)-induced neurite loss is associated with RIPK1 activation.
• To elucidate the molecular mechanisms underlying DHA's impact on neurite growth.

Main Methods:

• In vitro treatment of neurospheres (NE) with dehydroascorbic acid (DHA).
• Assessment of neurite shortening and branching.
• Analysis of RIPK1 activation.
• Inhibition studies using Necrostatin-1s and zVAD-FMK.

Main Results:

• Dehydroascorbic acid (DHA) treatment significantly reduced neurite length and branching in neurospheres.
• Early activation of RIPK1 was observed following DHA treatment.
• These effects were ameliorated by Necrostatin-1s and zVAD-FMK, indicating involvement of apoptotic pathways.

Conclusions:

• Dehydroascorbic acid (DHA) impairs neurite growth and branching in vitro.
• DHA-induced neurite damage is mediated by RIPK1 activation and subsequent caspase-dependent cell death.
• This suggests a novel mechanism for vitamin C's oxidized form in neurodegeneration.