About this episode

This episode discusses a study on a compound that halts upper motor neuron degeneration related to ALS by restoring mitochondrial and endoplasmic reticulum integrity.

**Paper:** [Improving mitochondria and ER stability helps eliminate upper motor neuron degeneration that occurs due to mSOD1 toxicity and TDP‐43 pathology](https://doi.org/10.1002/ctm2.336) **Authors:** Barış Genç, Mukesh Gautam, Öge Gözütok, Ina Dervishi, Santana Sanchez, et al. **Journal:** Clinical and Translational Medicine, 2021 **Why it matters:** NU-9 is the first compound shown to halt upper motor neuron degeneration — the cortical neurons whose loss defines ALS, primary lateral sclerosis, and hereditary spastic paraplegia — by physically restoring the structural integrity of mitochondria and the endoplasmic reticulum in living animals. **Summary** Upper motor neurons (UMNs), the cortical cells that issue commands for voluntary movement, degenerate in ALS, primary lateral sclerosis (PLS), and hereditary spastic paraplegia (HSP), yet have been largely overlooked in drug development because they are difficult to isolate and monitor in vivo. To address this, the researchers crossed disease mouse models — one driven by misfolded SOD1 protein (mSOD1) toxicity, another by TDP-43 pathology — with a UCHL1-eGFP reporter line that labels UMNs with green fluorescent protein…

People in this episode

Host: Raymond Ruff

Topics covered

• mitochondria
• upper motor neuron degeneration
• ALS
• TDP-43 pathology
• mSOD1 toxicity
• drug development

Keywords

• ALS
• upper motor neurons
• mSOD1
• TDP-43
• mitochondria
• drug development
• neurodegeneration

Mentioned in this episode

Organizations: Clinical and Translational Medicine

Books & works: Improving mitochondria and ER stability helps eliminate upper motor neuron degeneration that occurs due to mSOD1 toxicity and TDP‐43 pathology

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