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Krasnow Institute > Monday Seminars > Abstracts Molecular Alterations In Alzheimer's Disease: Studies in Fibroblasts and Neuronal Cells Rene Etcherberrigarray Several alterations have been described in fibroblasts of Alzheimer's disease (AD) patients including alterations in calcium regulation, protein kinase C (PKC) and potassium (K+) channels. Potassium channel dysfunction was demonstrated both directly using patch-clamp and indirectly using calcium imaging. Studies have also found reduced levels of the -isoform of PKC in brains and fibroblasts of AD patients. Since PKC is known to regulate ion channels, we studied K+ channel activity in fibroblasts from AD patients in the presence of (2S, 5S)-8-(1-decynyl) benzolactam V (BL), a novel , isozyme-selective activator of PKC. We present evidence for restoration of normal K+ channel function, as measured by TEA-induced [Ca2+]i elevations, due to activation of PKC with this BL. Immunoblotting analyses using an isozyme-specific PKC antibody confirm that BL-treated fibroblasts of AD patients show increased PKC activation. The present study suggests that PKC activator based restoration of K+ channels may offer another attractive approach to the investigation of AD pathophysiology which in turn could lead to the development of a valuable model for AD therapeutics.
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