Alejandro Lopez, a graduate research assistant at the Bowles Center for Alcohol Studies, has just discovered a new mechanism for allopregnanolone inhibition of inflammatory signaling.
Allopregnanolone inhibits binding of lipopolysaccaride (LPS) to it’s binding site in the binding pocket of the toll-like receptor: Myeloid differentiation factor-2 (TLR4:MD2) protein complex with nanomolar affinity. Such high affinity suggests that endogenous levels of allopregnanolone are sufficient to inhibit inflammatory TLR signaling in healthy humans.
Lopez also found that allopregnanolone blocks other components of the TLR4 activation mechanism in the brain of alcohol-preferring P rats, suggesting this might contribute to its ability to reduce excessive drinking in these rats. The discovery was published in BIomolecules last month: Lopez_Biomolecules_2024.
Lopez is a member of the A. Leslie Morrow Lab.