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What are the specific design principles for small molecules that can selectively modulate pathological vs. physiological TDP-43 phase separation?
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medicinal chemistry
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The debate identified that TDP-43 undergoes both normal and pathological phase separation, but no clear molecular criteria were established for designing therapeutics that preserve normal function while preventing aggregation. This represents a critical gap for rational drug design.
Source: Debate session sess_sda-2026-04-01-gap-006 (Analysis: sda-2026-04-01-gap-006)