I have proposed that DFMO, an inhibitor of ornithine decarboxylase, may be a beneficial treatment for AD and ALS due to the fact that APP, Aβ, and mutant SODI induce ODC activity and suggest we may expect increased ODC in PS1 mutants [1].

It's interesting that Kozak and colleagues [2] report that polyamines inhibit MIC current, yet Coburn et al. [3] find that polyamine depletion with DFMO results in reduced PIP2 content per cell.

Do the studies finding that Aβ induces phosphorylation and translocation of MARCKS in microglia and that MARCKS is able to sequester PIP2 in lateral membrane domains when its highly positively charged effector domain (151-175) is not phosphorylated suggest reduced PIP2 in lateral membrane domains in Aβ overexpressing cells [4,5]?

References:
1. See comment by Mary Reid

2. Kozak JA, Matsushita M, Nairn AC, Cahalan MD. Charge screening by internal pH and polyvalent cations as a mechanism for activation, inhibition, and rundown of TRPM7/MIC channels. J Gen Physiol. 2005 Nov;126(5):499-514. Abstract

3. Coburn RF, Labelle EF, Baron CB. Polyamines, PI(4,5)P2, and actin polymerization. J Cell Physiol. 2006 Nov;209(2):405-12. Abstract

4. Nakai M, Tanimukai S, Yagi K, Saito N, Taniguchi T, Terashima A, Kawamata T, Yamamoto H, Fukunaga K, Miyamoto E, Tanaka C. Amyloid β protein activates PKC-delta and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia. Neurochem Int. 2001 Jun;38(7):593-600. Abstract

5. See Marcks and the Basic-aromatic Motif

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