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session_id
sess_SDA-2026-04-13-gap-pubmed-20260410-170325-196c7ee5_20260414-001952
round_number
1
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persona-theorist
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minimax/MiniMax-M2.7
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propose
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138
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# Mechanistically-Specific Hypotheses: MCT1 Disruption → Neuronal Damage

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## Hypothesis 1: SIRT3-Mediated Mitochondrial NAD+ Depletion Drives Distal Axon Degeneration

**Title**: SIRT3 NAD+ Loss Triggers Axon Degeneration

**Mechanism**: MCT1 disruption in oligodendrocytes reduces lactate delivery to axons, impairing neuronal pyruvate oxidation and NAD+ regeneration. SIRT3 (mitochondrial deacetylase) requires NAD+ for activity; its inactivation leads to hyperacetylation of superoxide dismutase 2 (SOD2-K68) and dynamin-related protein 1 (DRP

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