A new target emerges from the single-cell map of Alzheimer’s disease
A comprehensive single-cell analysis of Alzheimer’s disease (AD) brain tissue has identified a promising new therapeutic target. Researchers integrated single-cell RNA sequencing and spatial transcriptomics data from AD cortical regions to computationally screen for repurposable drugs. The histone deacetylase inhibitor Trichostatin-A (TSA) emerged as the top candidate, demonstrating a protective effect against amyloid-beta toxicity in human neuron models. Crucially, the study pinpointed the gene DISC1 (Disrupted-In-Schizophrenia 1) as a convergent factor, uniquely upregulated in TSA-protected neurons and in specific, resilient neuronal and microglial subpopulations in AD brains. The findings suggest DISC1 mediates neuroprotection by regulating pathways involved in synaptic plasticity and mitochondrial function.
Why it might matter to you: This research shifts the focus from broad pathological hallmarks to specific, druggable pathways within defined cell populations, offering a more precise framework for therapeutic development. For professionals tracking neurodegeneration, the identification of DISC1 provides a novel mechanistic link between epigenetic modulation, synaptic integrity, and neuronal survival, potentially opening a new avenue for disease-modifying strategies. It underscores the power of high-resolution molecular profiling to reveal convergent targets that might be missed in bulk-tissue analyses.
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