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andrush05.bsky.social

@andrush05.bsky.social

Reposted by @andrush05.bsky.social

Carlos A. Sánchez León @carlosasleon.bsky.social · 13/09/2026

PREPRINT 🚨 You know that feeling when you're jamming out to your favorite song (say, La Macarena 💃) and suddenly it skips, or a completely random remix drops out of nowhere? That everyday surprise tells us something profound about how our brain works! 1/24

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andrush05.bsky.social @andrush05.bsky.social · 25/04/2025

This shows the power of cell-type-specific RNA profiling to uncover hidden vulnerabilities. EPAC2 inhibition could be a game-changer for FXS.

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andrush05.bsky.social @andrush05.bsky.social · 25/04/2025

And it worked. ✨ Restored cortical circuit function ✨ Ameliorated sensory behavioral phenotypes Targeting EPAC2 rescued key Fragile X features — offering a new therapeutic path forward! 🔥

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andrush05.bsky.social @andrush05.bsky.social · 25/04/2025

EPAC2, a cAMP-activated synaptic regulator, became our focus. We tested whether blocking EPAC2 could fix the circuit deficits. Using ESI-05, a selective EPAC2 inhibitor, we treated Fmr1 KO mice. 🧪

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andrush05.bsky.social @andrush05.bsky.social · 25/04/2025

Of hundreds of differentially expressed genes (DEGs), only 194 were shared across both neuron types. Amazingly, just one gene — Rapgef4 (Epac2) — was a brain-enriched ASD risk gene and a direct FMRP target. 🧬

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andrush05.bsky.social @andrush05.bsky.social · 25/04/2025

Using cell type-specific RNA-seq in Fmr1 knockout (KO) mice, we found opposite effects: genes were upregulated in excitatory neurons but downregulated in PV inhibitory neurons. Dramatic shifts in brain wiring.

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andrush05.bsky.social @andrush05.bsky.social · 25/04/2025

www.biorxiv.org/content/10.1... Excited to share my postdoctoral work! We mapped how loss of FMRP alters excitatory and inhibitory neurons in Fragile X Syndrome (FXS), the leading monogenic cause of autism. Huge molecular divergence — and a new therapeutic target! 🧵

biorxiv.org

Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of Fragile X mice and identifies EPAC2 as a therapeutic target.

Symptoms of Fragile X Syndrome (FXS), the leading monogenic cause of intellectual disability and autism, are thought to arise from an excitation/inhibition (E/I) imbalance. Here, we leverage cell type...

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andrush05.bsky.social @andrush05.bsky.social · 25/04/2025

www.biorxiv.org/content/10.1...

biorxiv.org

Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of Fragile X mice and identifies EPAC2 as a therapeutic target.

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