Proteostasis failure and mitochondrial dysfunction contribute to chromosomal instability-induced microcephaly - PubMed
7 hours ago
- #microcephaly
- #chromosomal instability
- #mitochondrial dysfunction
- Mosaic variegated aneuploidy (MVA) is a rare congenital disorder causing microcephaly due to chromosomal abnormalities.
- A Drosophila model was created to study microcephaly by depleting a spindle assembly checkpoint (SAC) gene in neural stem cells (NSCs).
- Loss of stemness in NSCs, leading to reduced neurons and glial cells, is a key factor in MVA.
- Complex aneuploidies (unbalanced chromosome gains/losses) contribute to stemness loss, not just DNA damage or simple aneuploidies.
- Proteostasis failure and mitochondrial dysfunction worsen the impact of complex aneuploidies on stemness.
- Overexpression of ROS scavengers, mitochondrial chaperones, and apoptosis inhibition can mitigate aneuploidy's effects on brain size.