The generation of a pathogenic molecule through protein misfolding cycling amplification (PMCA) in the presence of phospholipid is reminiscent of the "globulomer" complex formed from Aβ and specific lipids (Barghorn et al., 2005). There may also be some relationship to the role of gangliosides in creation of a toxic Aβ moiety (Kakio et al., 2002; Yamamoto et al., 2007). Perhaps lipid-protein interactions play a general and critical role in the development of peptide misfolding disorders.

References:
Barghorn S, Nimmrich V, Striebinger A, Krantz C, Keller P, Janson B, Bahr M, Schmidt M, Bitner RS, Harlan J, Barlow E, Ebert U, Hillen H. 2005. Globular amyloid beta-peptide oligomer - a homogenous and stable neuropathological protein in Alzheimer's disease. J Neurochem. 95:834-847. Abstract

Kakio A, Nishimoto S, Yanagisawa K, Kozutsumi Y, Matsuzaki K., 2002, Interactions of amyloid beta-protein with various gangliosides in raft-like membranes: importance of GM1 ganglioside-bound form as an endogenous seed for Alzheimer amyloid. Biochemistry 41:7385-7390. Abstract

Yamamoto N, Matsubara E, Maeda S, Minagawa H, Takashima A, Maruyama W, Michikawa M, Yanagisawa K., 2007, A ganglioside-induced toxic soluble Abeta assembly. Its enhanced formation from Abeta bearing the Arctic mutation. J. Biol. Chem. 282:2646-2655. Abstract

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