Characterization of the influence of Amyloid β (1-42) By Way of Modeling Synaptic Cleft with an RC Electronic Circuit

Year 2021, Volume: 12 Issue: 1, 53 - 59, 13.01.2021

M. Emin Tağluk , İbrahim Işık

https://doi.org/10.24012/dumf.703270

Cited By: 1

Abstract

The research toward understanding the role of oligomeric amyloids in Alzheimer disease (AD) has gained a considerable attention in recent years. The information obtained in this direction showed that Amyloid Derived Diffusible Ligands (ADDLs) cause an ambiguous ions movements across lipid bilayers in plasma membrane and consequently alter its dielectric properties such as permeability. Nevertheless, how these amyloid protein selectively alters the permeability of cell membrane has not been noted down because none of specific receptor have been identified for ADDLs binding. As a result of the increase of cellular calcium level, local micromechanical properties of cells can change and thus induce reorganization of cytoskeletal structures that can cause neurodegenerative disorders such as AD. Therefore, in this study we have tried to specify the effect of alteration of permittivity and permeability of synaptic channel as modelling synaptic cleft by an RC circuit. By linking the electronic neuronal models that we have previously designed with the RC cleft model, when the information transferred from one neuron to another, the rate of error measured on the later neuron circuit with reference of the former one was determined with respect to the rate of change of R and C values individually. It was observed that C and R, and hence permeability of synaptic channel does effect the communication error. It is concluded that a healthy synaptic channel conserves optimum resistivity and capacity levels at which the inter-neuronal signalling is achieved at a minimum error. This results could be linked to hypothesizes that amyloids have a common feature in structuring channel-like concentrations which supported by their electrical activity as well as the rate of permeability of Calcium like cautions.

Keywords

Alzheimer disease, Amyloid beta, Synaptic cleft

Supporting Institution

inonu university

Project Number

FDK-2019-1359

Thanks

This study is supported by the İnonu University Scientifics Researchers Project Department (BAP) under project ID: FDK-2019-1359.

References

• 1. Gong YS, Chang L, Viola KL, Lacor PN, Lambert MP, Finch CE, Krafft GA, Klein WL., “Alzheimer’s disease-affected brain: Presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss.” Proc Natl Acad Sci U S A 2003;100:10417–10422. [PubMed: 12925731]].
• 2. Sokolov Y, Ashot Kozak J, Kayed R, Chanturia A, Glabe CG, Hall JE., “Soluble amyloid oligomers increase bilayer conductance by altering dielectric structure.” J Gen Physiol 2006;128:637–647. [PubMed: 17101816]].
• 3. Green JD, Kreplak L, Goldsbury C, Blatter XL, Stolz M, Cooper GS, Seelig A, Kist-Ler J, Aebi U., “Atomic force microscopy reveals defects within mica supported lipid bilayers induced by the amyloidogenic human amylin peptide.”, J Mol Biol 2004;342:877–887. [PubMed: 15342243].
• 4. Kayed R, Sokolov Y, Edmonds B, MacIntire TM, Milton SC, Hall JE, Glabe CG., “Permeabilization of lipid bilayers is a common conformation-dependent activity of soluble amyloid oligomers in protein Mis-folding diseases”,. J Biol Chem. 2004, 279(45):46363-6.
• 5. Lin H, Bhatia R, Lal R. Amyloid beta protein forms ion channels: implications for Alzheimer’s disease pathophysiology. Faseb J 2001;15:2433–2444. [PubMed: 11689468].
• 6. Lin H, Zhu YWJ, Lal R. Amyloid beta protein (1–40) forms calcium-permeable, Zn2+-sensitive channel in reconstituted lipid vesicles. Biochemistry 1999;38:11189–11196. [PubMed: 10460176].
• 7. Quist A, Doudevski I, Lin H, Azimova R, Ng D, Frangione B, Kagan B, Ghiso J, Lal R. Amyloid ion channels: A common structural link for protein-misfolding disease. Proc Natl Acad Sci U S A 2005;102:10427–10432. [PubMed: 16020533].
• 8. Arispe N. Architecture of the Alzheimer’s A beta P ion channel pore. J Membr Biol 2004;197:33–48. [PubMed: 15014916].
• 9. Ratnesh Lal, Hai Lin, and Arjan P. Quist, “Amyloid beta ion channel: 3D structure and relevance to amyloid channel paradigm.” Biochim Biophys Acta. 2007, 1768(8): 1966–1975. doi:10.1016/j.bbamem.2007.04.021.
• 10. Thomas T, Thomas G, McLendon C, Sutton T, Mullan M. “Beta amyloid mediated vasoactivity and vascular endothelial damage.” Nature 1996;380:168–171. [PubMed: 8600393].
• 11. Mattson MP. “Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives.” Physiol Rev 1997;77:1081–1132. [PubMed: 9354812].
• 12. Mobley DL, Cox DL, Singh RRP, Maddox MW, Longo ML. Modeling amyloid beta-peptide insertion into lipid bilayers. Biophys J 2004;86:3585–3597. [PubMed: 15189856].
• 13. Durell SR, Guy HR, Arispe N, Rojas E, Pollard HB. Theoretical-Models of the Ion-Channel Structure of Amyloid Beta-Protein. Biophys J 1994;67:2137–2145. [PubMed: 7535109].
• 14. Tsigelny IF, Bar-On P, Sharikov Y, Crews L, Hashimoto M, Miller MA, Keller SH, Platoshyn O, Yuan JXJ, Masliah E. Dynamics of alpha synuclein aggregation and inhibition of pore-like oligomer development by beta synuclein. FEBS J 2007;274:1862–1877. [PubMed: 17381514].
• 15. Zakharov SD, Hulleman JD, Dutseva EA, Antonenko YN, Rochet JC, Cramer WA, “Helical alpha-synuclein forms highly conductive ion channels” Biochemistry. 2007 Dec 18;46(50):14369-79. Epub 2007 Nov 22.
• 16. Savtchenko, L. P., Korogod, S. M. & Rusakov, D. A. Electrodiffusion of synaptic receptors: a mechanism to modify synaptic efficacy? Synapse 35, 26-38 (2000).
• 17. Isaev, D. et al. Role of extracellular sialic acid in regulation of neuronal and network excitability in the rat hippocampus. J Neurosci 27, 11587-11594 (2007).
• 18. “Beta-amyloid and the amyloid hypothesis”, Alzhemier association, 888-372-3900, Alz.org, TS-0039 | Updated August 2019.
• 19. Sara H. Mokhtar,Maha M. Bakhuraysah, David S. Cram, and Steven Petratos, “The Beta-Amyloid Protein of Alzheimer’s Disease: Communication Breakdown by Modifying the Neuronal Cytoskeleton”, Hindawi Publishing Corporation International Journal of Alzheimer’s Disease Volume 2013, Article ID 910502, 15 pages http://dx.doi.org/10.1155/2013/910502.
• 20. M. E. Tagluk, “A New Dynamic Electronic Model of Neuron’s Membrane”, Anatolian Journal of Computer Sciences, Volume 3, Issue 1, 2018, Page 1-6.
• 21. M Emin Tagluk, Ibrahim Isik, “Communication in nano devices: Electronic based biophysical model of a neuron” Nano Communication Networks, Vol 19, pp 134-147, 2019.
• 22. E. Isik, I. Isik, M. E Tagluk, “Effect of Aβ on the Probability of Molecule Reception in MCvD”, ICONDATA’20 June 25 - 28, 2020 in Istanbul, Turkey.