Rac in the act of forgetting.
Cell. 2010 Feb 19;140(4):456-8.
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This fly paper catches genetic evidence that Rac inhibition slows memory decay, constitutively increased Rac activation accelerates memory decay, and that cofilin hyperactivation gives rise to the same phenotype as seen with Rac inhibition. The authors conclude that the “Rac-regulated PAK/LIMK/cofilin pathway might be critical in influencing memory decay.” The specificity for Rac activation defects in an active forgetting process relevant to stronger longer-term memory with repetitive learning is novel and interesting. To the extent that these observations can be generalized to mammals, they may relate to the acute and chronic soluble Aβ oligomer-induced dysregulation of Rac/PAK/LIMK1/cofilin signaling (Zhao et al 2006., Ma et al., 2008, Gureviciene et al., and other refs) with LTP deficits and enhanced LTD (Li et al., 2009) and synapse loss (Freir et al., 2010). Conversely, memory consolidation is also impaired along with enhanced LTP and reduced LTP when PAK is selectively genetically inhibited in forebrain (Hayashi et al., 2004).
Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D.
Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake.
Neuron. 2009 Jun 25;62(6):788-801.
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Neuron. 2004 Jun 10;42(5):773-87.
Gureviciene I, Ikonen S, Gurevicius K, Sarkaki A, van Groen T, Pussinen R, Ylinen A, Tanila H.
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Balducci C, Beeg M, Stravalaci M, Bastone A, Sclip A, Biasini E, Tapella L, Colombo L, Manzoni C, Borsello T, Chiesa R, Gobbi M, Salmona M, Forloni G.
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Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2295-300.
Freir DB, Fedriani R, Scully D, Smith IM, Selkoe DJ, Walsh DM, Regan CM.
Abeta oligomers inhibit synapse remodelling necessary for memory consolidation.
Neurobiol Aging. 2010 Jan 22;
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