Document Type
Article
Language
eng
Publication Date
12-2017
Publisher
Elsevier
Source Publication
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Source ISSN
0167-4889
Abstract
The ability of beta-amyloid peptide (Aβ) to disrupt the plasma membrane through formation of pores and membrane breakage has been previously described. However, the molecular determinants for these effects are largely unknown. In this study, we examined if the association and subsequent membrane perforation induced by Aβ was dependent on GM1levels. Pretreatment of hippocampal neurons with D-PDMP decreased GM1 and Aβ clustering at the membrane (Aβ fluorescent-punctas/20 μm, control = 16.2 ± 1.1 vs. D-PDMP = 6.4 ± 0.4, p < 0.001). Interestingly, membrane perforation with Aβ occurred with a slower time course when the GM1 content was diminished (time to establish perforated configuration (TEPC) (min): control = 7.8 ± 2 vs. low GM1 = 12.1 ± 0.5, p < 0.01), suggesting that the presence of GM1 in the membrane can modulate the distribution and the membrane perforation by Aβ. On the other hand, increasing GM1 facilitated the membrane perforation (TEPC: control = 7.8 ± 2 vs. GM1 = 6.2 ± 1 min, p < 0.05). Additionally, using Cholera Toxin Subunit-B (CTB) to block the interaction of Aβ with GM1 attenuated membrane perforation significantly. Furthermore, pretreatment with CTB decreased the membrane association of Aβ (fluorescent-punctas/20 μm, Aβ: control = 14.8 ± 2.5 vs. CTB = 8 ± 1.4, p < 0.05), suggesting that GM1 also plays a role in both association of Aβ with the membrane and in perforation. In addition, blockade of the Aβ association with CTB inhibited synaptotoxicity. Taken together, our results strongly suggest that membrane lipid composition can affect the ability of Aβ to associate and subsequently perforate the plasma membrane thereby modulating its neurotoxicity in hippocampal neurons.
Recommended Citation
Fernandez-Perez, E. J.; Sepulveda, Fernando; Peoples, Robert W.; and Aguayo, Luis G., "Role of Membrane GM1 on Early Neuronal Membrane Actions of Aβ During Onset of Alzheimer's Disease" (2017). Biomedical Sciences Faculty Research and Publications. 176.
https://epublications.marquette.edu/biomedsci_fac/176
Comments
Accepted version. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol. 1863, No. 12 (December 2017): 3105-3116. DOI. © 2017 Elsevier B.V. Used with permission.