STMN2 protein depletion via translation deficits and stress granules in amyotrophic lateral sclerosis - PubMed
4 hours ago
- #protein translation
- #neurodegeneration
- #stress granules
- STMN2 protein depletion in ALS can occur via translation deficits and stress granules independently of TDP-43 nuclear condensation.
- Under acute high-magnitude stress, STMN2 is suppressed through proteasomal degradation, phosphorylation, and translation repression by stress granules.
- STMN2 protein level is highly sensitive to chronic translation deficits, such as those from prolonged low-grade stress.
- Low pre-stress STMN2 sensitizes neuronal cells to stress-induced apoptosis, while moderately increased STMN2 is protective under stress.
- STMN2 mRNA is upregulated in ALS-FUS models, possibly compensating for translation and stress granule defects, and also in spared CNS regions in ALS-TDP.
- The study highlights dysregulation of translation and stress granules as common denominators in neurodegeneration affecting STMN2.