Langmade SJ, Gale SE, Frolov A, Mohri I, Suzuki K, Mellon SH, Walkley SU, Covey DF, Schaffer JE, Ory DS. Pregnane X receptor (PXR) activation: A mechanism for neuroprotection in a mouse model of Niemann-Pick C disease. Proc Natl Acad Sci U S A. 2006 Aug 29; PubMed.
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College of Medicine, University of Arizona
The findings of Langmade, Gale, and colleagues, that allopregnanolone delayed progression of pathology and promoted survival, potentially through a PXR receptor-mediated mechanism, has exciting mechanistic and therapeutic implications. Mechanistically, allopregnanolone activation of the PXR receptor, leading to an increase in the cytochrome P450 enzyme CYP3A13, suggests a novel mechanism of allopregnanolone neuroprotection that brings the benefits of "liver" detox to the brain. Therapeutically, activating “liver-type” detoxification in brain may be a broad-spectrum strategy for promoting neurological health and defense against neurodegenerative insults.
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