IRE1 regulates the proteostasis of TDP-43/TARDBP in ALS/FTD through ribosome-associated quality control - PubMed
2 hours ago
- #RQC
- #TDP-43
- #IRE1
- IRE1 suppresses TDP-43 protein levels and is identified as a key regulator in ALS/FTD pathology.
- Ribosome-associated quality control (RQC) factors prevent excessive TDP-43 accumulation and reduce cellular toxicity.
- IRE1 promotes degradation of aberrant TDP-43 via RQC, both by enhancing Clbn/NEMF transcription and interacting with it.
- Activation of IRE1, through expression or drugs, alleviates TDP-43 pathology and improves cognitive function in mouse models.
- The study suggests IRE1 as a potential therapeutic target for ALS/FTD by regulating TDP-43 proteostasis.