Overview of Interests
Ned Porter studies an inborn error of metabolism, Smith-Lemli-Opitz syndrome (SLOS). The main metabolic defect, a reduced level of cholesterol and an increased level of dehydrocholesterol, primarily manifests itself with a range of brain abnormalities that include a combination of microcephaly, myelin maturation delay, lyssencephaly, agenesis/hypoplasia of corpus callosum, hypoplastic cerebellum, or other CNS deficits. Patients with SLOS also exhibit intellectual disability and autism-like symptoms.
Our preliminary findings and recently published data show that a) dehydrocholesterol (7-DHC) is, to our knowledge, the most reactive lipid toward free radical peroxidation that has been studied to date; b) the peroxidation products formed from 7-DHC can be understood based upon established chemical mechanisms; c) some of our newly discovered 7-DHC oxidation products are measurable both in a Dhcr7-deficient neuronal cells line and in the brain of Dhcr7-KO mice while these products are not present in control cells or mice; d) Dhcr7-KO mice exhibit higher levels of oxidative stress compared to controls; e) Dhcr7-deficient neuronal cells are susceptible to oxidative stress and lipid peroxidation initiated by peroxides or 6-hydroxydopamine; and f) pyridinol and pyrimidinol compounds constitute a new class of powerful antioxidants that we have discovered, and these compounds inhibit the formation of 7-DHC oxidation products in SLOS cells.
Porter’s current studies will lead to an understanding of the pathophysiological events underlying SLOS and move research toward the design of knowledge-based therapeutic approaches.
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