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Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents
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tRNA modification enzyme-dependent redox homeostasis regulates synapse formation and memory
Kimberly R Madhwani1, Shanzeh Sayied2, Carlson H Ogata3
1Neuroscience Graduate Program, Brown University, Providence, RI, USA.
Biorxiv : the Preprint Server for Biology
|November 28, 2023
Summary
ALKBH8, a tRNA modifying enzyme, is crucial for brain health, regulating oxidative stress to support learning and memory. Antioxidants may treat intellectual disability linked to ALKBH8 dysfunction.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- Post-transcriptional RNA modification regulates gene expression.
- ALKBH8 (Alkbh8 homolog 8) is a tRNA modifying enzyme essential for selenoprotein synthesis and redox homeostasis.
- Pathogenic variants in ALKBH8 are linked to intellectual disability, but its nervous system role is unclear.
Conclusions:
- ALKBH8 plays a critical role in maintaining redox homeostasis in the brain by regulating tRNA modification and selenoprotein synthesis.
- Oxidative stress resulting from ALKBH8 dysfunction contributes to synaptic abnormalities and cognitive impairments.
- Antioxidant therapies show promise for treating intellectual disabilities associated with ALKBH8 variants.
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