Membrane-Related Diseases

  • Mohammad AshrafuzzamanEmail author
  • Jack Tuszynski
Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)


Life starts with a single cell, but the cell is also where the origin of most pathological changes and disorders can be traced. Disease states can, in most cases, be linked to the abnormal functioning of specific organs. A living cell is the fundamental unit where most of these abnormalities happen and where they are initiated. That is why a cell is also the ultimate target for the action of most drugs. Cancer, Alzheimer’s disease, Parkinson’s disease, various infectious diseases, etc. originate in individual cellular compartments, including the membrane. This chapter will be dedicated to a better understanding of the membrane’s involvement in diseases, and disease treatment using drugs targeting cell membranes. Several examples will be used for illustration purposes. However, due to the book’s subject matter, we will concentrate on the scientific aspects of a few of the membrane-based diseases, leaving the medical issues aside. Below, we list several diseases that are either directly or indirectly related to membrane properties and their abnormalities.


Cystic Fibrosis Transmembrane Conductance Regulator Duchenne Muscular Dystrophy Bovine Spongiform Encephalopathy Duchenne Muscular Dystrophy Griscelli Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
  2. 2.
  3. 3.
    “Prion Diseases”. US Centers for Disease Control. 2006-01-26. Retrieved 2010-02-28.Google Scholar
  4. 4.
    Aguzzi, A.: Unraveling prion strains with cell biology and organic chemistry. Proc. Nat. Acad. Sci. USA 105(1), 11–2 (2008) doi: 10.1073/pnas.0710824105. PMC 2224168. PMID 18172195. Retrieved 2010-02-28
  5. 5.
    Ashrafuzzaman, M., Tseng, C.Y., Kapty, J., Mercer, J.R., and Tuszynski, J.A.: Computationally designed DNA aptamer specific for phosphatidylserine lipid (submitted). (2011)Google Scholar
  6. 6.
    Belay, E.D.: Transmissible spongiform encephalopathies in humans. Annual Review of Microbiology 53, 283–314. (1999)Google Scholar
  7. 7.
    Berezovska, O., Lleo, A., Herl, L.D., Frosch, M.P., Stern, E.A., Bacskai, B.J., Hyman, B.T.: Familial Alzheimer’s disease presenilin 1 mutations cause alterations in the conformation of presenilin and interactions with amyloid precursor protein. J Neurosci. 25(11), 3009–17 (2005)Google Scholar
  8. 8.
    Bertram, L., Tanzi, R. E.: Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nature reviews. Neuroscience 9 (10): 768–778 (2008) doi: 10.1038/nrn2494. PMID 18802446. edit
  9. 9.
    Blankenberg, F.G.: Imaging the molecular signatures of apoptosis and injury with radiolabeled annexin V. Proc Am Thorac Soc. 6(5):469–76 (2009)Google Scholar
  10. 10.
    Blankenberg, F.G.: In vivo imaging of apoptosis. Cancer Biol Ther. 7(10):1525–32 (2008)Google Scholar
  11. 11.
    Covas, D. T.: Effects of hydroxyurea on the membrane of erythrocytes and platelets in sickle cell anemia. Haematologica 89, 273–280 (2004)Google Scholar
  12. 12.
    Craddock, T.J.A., Tuszynski, J.A., Chopra, D., Casey, N., Goldstein, L.E., Hameroff, S.R., and Tanzi, R.: The Zinc Dyshomeostasis Hypothesis of Alzheimer's Disease. PLoS ONE 7(3):e33552 (2012) Google Scholar
  13. 13.
    Elmore, S.: Apoptosis: a review of programmed cell death. Toxicol Pathol. 35:495–516 (2007)Google Scholar
  14. 14.
    Ertekin-taner, N.: Genetics of Alzheimer’s disease: a centennial review. Neurologic clinics 25 (3): 611–667 (2007) doi: 10.1016/j.ncl.2007.03.009. PMC 2735049. PMID 17659183
  15. 15.
    Futerman, A. H.& van Meer, G.: The cell biology of lysosomal storage disorders. Nature Rev. Mol. Cell Biol. 5, 554–565 (2004)Google Scholar
  16. 16.
    Gurtovenko, A.A., and Anwar, J. Interaction of Ethanol with Biological Membranes: The Formation of Non-bilayer structures within the Membrane Interior and their Significance. J. Phys. Chem. B 113 (7), 1983–1992 (2009)Google Scholar
  17. 17.
    Hanahan, D., Weinber, R.A.: The hallmarks of cancer. Cell 100, 57–70 (2000)Google Scholar
  18. 18.
    Horisberger, J. D.: ENaC-CFTR interactions: the role of electrical coupling of ion fluxes explored in an epithelial cell model; Pflugers Arch. Jan 445(4), 522–8 (2003)Google Scholar
  19. 19.
    James, T. L., Liu, H., Ulyanov, N. B., Farr-Jones, S., Zhang, H., Donne, D. G. et al.: Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform. Proc. Natl Acad. Sci. USA, 94, 10086–10091 (1997)Google Scholar
  20. 20.
    Jerabek, H., Pabst, G., Rappolt, M., and Stockner, T.: Membrane-Mediated Effect on Ion Channels Induced by the Anesthetic drug Ketamine. J. Am. Chem. Soc. 132 (23), 7990–7997 (2010)Google Scholar
  21. 21.
    Kerr, J.F., Wyllie, A.H. and Currie, A.R.: Apoptosis – a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer. 4, 239–257 (1972)Google Scholar
  22. 22.
    Kraulis, P. J.: MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallog. 24, 946–950 (1991)Google Scholar
  23. 23.
    Lahorte, C. et al.: Apoptosis-detecting radio ligands: current state of the art and future perspectives. European J. of Nuclear Med and, Mol Imaging. 31, 887–919 (2004)Google Scholar
  24. 24.
    Levy-Lahad, E., Wasco, W., Poorkaj, P., et al.: Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 269 (5226), 973–7 (1995) Bibcode 1995Sci...269.973L. doi: 10.1126/science.7638622. PMID 7638622Google Scholar
  25. 25.
    Li, X., Link, J.M., Stekhova, S., Yagle, K.J., Smith, C., Krohn, K.A. and Tait, J.F.: Site specific labeling of annexin V with F-18 for apoptosis imaging. Bioconjug Chem. 19, 1684–1688 (2008)Google Scholar
  26. 26.
    Maher, J. J.: Exploring Alcohol’s Effects on Liver Function. Alcohol Health& Research World Vol. 21 (1), 1–12 (1997)Google Scholar
  27. 27.
    Martin, S.J., Reutelingsperger, C.P., McGahon, A.J., Rader, J.A., van Schie, R.C., LaFace, D.M., Green, D.R.: Early Redistribution of Plasma Membrane phosphatidylserine Is a General Feature of Apoptosis Regardless of the Initiating Stimulus: Inhibition by Overexpression of B\(Cl^-\)2 and Abl. J. Exp. Med. 182, 1545–1556 (1995)Google Scholar
  28. 28.
    McNeil, P. L.& Steinhardt, R. A.: Plasma membrane disruption: repair, prevention, adaptation. Ann. Rev. Cell Dev. Biol. 19, 697–731 (2003)Google Scholar
  29. 29.
    Murakami, Y., Takamatsu, H., Taki, J., Tatsumi, M., Noda, A., Ichise, R., Tait. J.F. and Nishimura, S.: 18F-labeled annexin V: a PET tracer for apoptosis imaging. Eur J Nucl Med Mol Imaging. 31, 469–474 (2004)Google Scholar
  30. 30.
    Nakai, T., Yamasaki, A., Sakaguchi, M., Kosaka, K., Mihara, K., Amayai, Y., and Miura, S.: Membrane Topology of Alzheimer’s Disease-related Presenilin 1. J. Biol. Chem. 274 (33), 23647–23658 (1999)Google Scholar
  31. 31.
    Oltersdorf, T. et al.: An inhibitor of B\(Cl^-\)2 family proteins induces regression of solid tumours. Nature 435, 677–681 (2005)Google Scholar
  32. 32.
    Petros, A.M., Nettesheim, D.G., Kim, D.H., Yoon, H.S., Swift, K., Matayoshi, E.D., Oltersdorf, T., Fesik, S.W.: Solution structure of the antiapoptotic protein b\(Cl^-\)2 Proc. Natl. Acad. Sci. USA 98, 3012–3017 (2001)Google Scholar
  33. 33.
    Petros, A.M., Oltersdorf, T., Fesik, S.W.: Structural biology of the B\(Cl^-\)2family of proteins. Biochem. et Biophys. Acta 1644, 83–94 (2004)Google Scholar
  34. 34.
    Rastogi, R.P., Richa, and Sinha, R.P.: Apoptosis: molecular mechanisms and pathogenicity. EXCLI Journal. 8, 155–181 (2009) ISSN 1611–2156Google Scholar
  35. 35.
    Reed, J.C., Tomaselli, K.J.: drug discovery opportunities from apoptosis research. Curr Opin Biotechnol. 11, 586–92 (2000)Google Scholar
  36. 36.
    Robbins, S.L., Cotran, R.S., Kumar, V., Collins, T., ed.: Robbins pathologic basis of disease. Philadelphia: Saunders. (1999) ISBN 0-7216-7335-XGoogle Scholar
  37. 37.
    Robinson, P.J. and Pinheiro, T.J.T.: phospholipid Composition of Membranes Directs Prions Down Alternative Aggregation Pathways. Biophys. J. 98 April 1520–1528 (2010)Google Scholar
  38. 38.
    Sanghera, N. and Pinheiro, T.J.T.: Binding of prion protein to lipid membranes and implications for prion conversion. J. Mol. Biol. 315(5), 1241–1256 (2002)Google Scholar
  39. 39.
    Sekulic, A. et al.: Malignant Melanoma in the 21st Century: The Emerging Molecular Landscape. Mayo Clinic Proceedings 83, 825–846 (2008)Google Scholar
  40. 40.
    Smrz, D., Lebduska, P., Dráberová, L., Korb, J. and Dráber, P.: Engagement of phospholipid scramblase 1 in activated cells: implication for phosphatidylserine externalization and exocytosis. J Biol Chem. 283(16), 10904–18 (2008)Google Scholar
  41. 41.
    Sohma, Y., Gray, M.A., Imai, Y., Argent, B.E.: \(HCO_3^-\) transport in a mathematical model of the pancreatic ductal epithelium. J Member Biol. 176(1), 77–100 (2000)Google Scholar
  42. 42.
    Stellar, H.: Mechanisms and Genes of Cellular Suicide. Science 267, 1445–1449 (1995)Google Scholar
  43. 43.
    Suzuki, M., Youle, R.J., Tjandra, N.: structure of Bax: coregulation of dimer formation and intracellular localization. Cell 103, 645–654 (2000)Google Scholar
  44. 44.
    Terama, E., Ollila, O. H.S., Salonen, E., Rowat, A.C., Trandum, C., Westh, P., Patra, M., Karttunen, M., and Vattulainen, I.: Influence of Ethanol on Lipid Membranes: From Lateral pressure Profiles to Dynamics and Partitioning. J. Phys. Chem. B 112(13), 4131–4139 (2008)Google Scholar
  45. 45.
    Toretsky, J., Levenson, A., Weinberg, I.N., Tait, J.F., Uren, A. and Mease, R.C.: Preparation of F-18 labeled annexin V: a potential PET radiopharmaceutical for imaging cell death. Nucl Med Biol. 31(6), 747–52 (2004)Google Scholar
  46. 46.
    Tse, C. et al.: ABT-263 A potent and orally bioavailable B\(Cl^-\)2 family inhibitor. Cancer Res. 68, 3421–3428 (2008)Google Scholar
  47. 47.
    Tseng, C.Y., Ashrafuzzaman, M., Mane, J., Kapty, J., Mercer, J. and Tuszynski, J.: Entropic Fragment-Based Approach to Aptamer. Chem Biol drug Des 78, 1–13 (2011)Google Scholar
  48. 48.
    van Delft, M.F. et al.: The BH3 mimetic ABT-737 targets selective B\(Cl^-\)2 proteins and efficiently induces apoptosis via Bak/Bax if M\(Cl^-\)1 is neutralized. Cancer Cell 10, 389–399 (2006)Google Scholar
  49. 49.
    van Engeland, M., Nieland, L.J.W., Ramaekers, F.C.S., Schutte, B., and Reutelingsperger, C.P.M.: Annexin V-Affinity Assay: A Review on an Apoptosis Detection System Based on phosphatidylserine Exposure Cytometry 31, 1–9 (1998)Google Scholar
  50. 50.
    Weinberg, R.A.: The biology of Cancer. Garlan Science, NY USA (2007)Google Scholar
  51. 51.
    Williamson, J., Goldman, J., Marder, K.: Genetic aspects of Alzheimer disease. The Neurologist 15(2), 80–86 (2009) doi: 10.1097/NRL.0b013e318187e76b. PMC 3052768. PMID 19276785. edit

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of Biochemistry, College of ScienceKing Saud UniversityRiyadhSaudi Arabia
  2. 2.Department of Physics,Cross Cancer InstituteUniversity of AlbertaEdmontonCanada

Personalised recommendations