Across ALS, stroke, and Alzheimer’s disease, researchers are exploring ways to protect neurons by targeting very different biological pathways. One new preclinical study found that sodium butyrate reduced toxic SOD1 protein aggregation and improved movement and nerve integrity in models of ALS. In a rat model of cerebral ischemia, high-dose MK-801 reduced early cortical injury even when mTOR-related signaling was suppressed, suggesting that other protective mechanisms may be involved.
A third study took a different approach, using large real-world health datasets to search for existing medications that might slow progression from mild cognitive impairment to Alzheimer’s disease or related dementias. Researchers identified 20 promising candidates for further study, though the findings do not establish that these drugs prevent dementia. Together, these studies show how neuroscience is advancing on several fronts, from targeting protein toxicity and limiting acute brain injury to finding new uses for existing medications.
1. The HDAC Inhibitor Butyrate Reduces SOD1 Aggregation and Improves Motor Function in C. elegans and Cellular Models of ALS
A new preclinical study found that sodium butyrate, a gut microbiome-derived metabolite and HDAC inhibitor, reduced toxic SOD1 protein aggregation in ALS models. It also improved movement, neuromuscular function, and axonal integrity in C. elegans, supporting further study of butyrate and related HDAC-targeting approaches for ALS.
2. High-Dose MK-801 Attenuated Early TTC-Defined Cortical Injury Even under the Conditions of Suppressed Rapamycin-Sensitive pS6 Signaling during Early Cerebral Ischemia–Reperfusion
In a rat model of cerebral ischemia, high-dose MK-801 reduced early cortical infarct size even when mTOR-related pS6 signaling was strongly suppressed. The findings suggest its neuroprotective effects may rely on pathways beyond mTORC1, although MK-801 itself is not considered suitable for clinical use because of toxicity concerns.
3. Discovering repurposable drugs for Alzheimer’s disease and related dementias: target trial emulation using decentralised real-world data
Researchers screened 181 commonly prescribed medications using large real-world health datasets and identified 20 drugs associated with a lower risk of progression from mild cognitive impairment to Alzheimer’s disease or related dementias. The findings do not prove these medications prevent dementia, but they highlight promising candidates for future clinical trials and drug-repurposing studies.
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