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NeurosciencePlanned2026

BMAA × TDP-43 flies

A two-hit model of ALS

Does a Florida cyanobacteria toxin tip ALS-model fruit flies into motor decline, and does L-serine block it?

Bar chart sketch: only flies with both the M337V mutation and BMAA cross the failure threshold
2×2×2genotype, toxin and L-serine
3readouts: climbing, TDP-43 localization, lifespan
7 daysof exposure, after raising the lines for 21

The question

Chronic low-dose BMAA in flies expressing human TDP-43 (wild-type and the M337V mutation), with L-serine as a possible block. The prediction is that neither hit is enough alone, and only flies with both the mutation and the toxin cross the failure threshold. There's no data yet: this is the plan.

TDP-43 in the wrong place: held in the nucleus when healthy, cleared into cytoplasmic clumps in disease.
TDP-43 in the wrong place: held in the nucleus when healthy, cleared into cytoplasmic clumps in disease.
How BMAA gets into proteins: charged by the alanine tRNA synthetase, not the serine one.
How BMAA gets into proteins: charged by the alanine tRNA synthetase, not the serine one.
Exposure protocol.
Exposure protocol.
The two-hit prediction, sketched.
The two-hit prediction, sketched.