Research Journal of Pharmacology and Pharmacodynamics

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Biochemical Origins of Alzheimer's Disease with Treatment Techniques


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1 Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, India
     

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Alzheimer's disease (AD) is a neurodegenerative disease caused by irregular protein formations in the brain leading to neuronal loss and ultimately affecting the patient's cognitive ability and memory. AD affects nearly 4.5 million Americans, and this number is expected to continue to rise. The pathological manifestations of AD occur in the neurons and are two-fold; the primary cause is the accumulation. β-amyloid (amyloid precursor protein) depositions, which aggregate into pathogenic plaques. The second is the accumulation of paired helical filaments that form into neurofibrillary tangles (NFTs). Amyloid precursor protein plaques result from the sequential cleavage of the amyloid precursor protein (APP) by β-secretase and γ-secretase. NFTs result from the hyperphosphorylation of tau, a stabilizing component of microtubules. Based on current understanding of the Amyloid precursor protein pathway, two major strategies will be discussed that aim at decreasing the deposition of Amyloid precursor protein plaques in the brain. In the first approach, non-streroidal anti-inflammatory drugs alter the APP cleavage site by β-secretase to produce less amyoidogenic plaques. A second method aims at inhibiting γ-secretase activity on APP through allosteric inhibition of ATP binding.
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  • Alzheimer's Association. www.alz.org. December 27, 2006.

  • Goedert M.; Grazia Spillantini M. Science. 2006, 314, 777-781.

  • Argellati, F.; Massone, S.; d'Abramo, C.; Marinari, U.M.; Pronzato, M.A.; Domenicotti, C.; Ricciarelli, R. IUBMB Life.2006, 58, 103-106.

  • Selkoe, D.J; Physiol. Rev. 2001, 81, 741-766.

  • Iwatsubo, T.; Mann, D.M.; Odaka, A.; Suzuki, N.; Ihara. Y. Ann Neurol. 1995, 37, 287-8.

  • Haass C; Hung AY; Schlossmacher MG; Teplow DB; Selkoe DJ. J Biol Chem, 1993, 268, 3021-3024.

  • Crowther, R.A.; Wischik, C.M. EMBO J. 1985, 4, 3661-3665.

  • Mandelkow, E.; Nature. 1999, 402, 588-589.

  • Patrick, G.N.; Zukerberg, L.; Nikolic, M.; de la Monte S.; Dikkesk, P.; Tsai, L.H. Nature. 402, 1999, 615-22.

  • Kusakawa, G.; Saito, T.; Onuki R.; Ishiguro, K.; Kishimoto, T.; Hisanaga, S; J. Biol Chem. 275. 2000, 17166-17172.

  • McCullagh, C.D.; Craig D.; McIlroy, S.P.; Passmore, A.P. Adv. In Psych. Treatment. 2001, 7, 24-31.

  • Mahley, R.W.; Weisgraber, K.H.; Huang, Y. Proc. Natl. Acad. Sci. USA. 2006, 103, 5644-5651.

  • Stittmatter, W.J.; Roses, A.D. Proc. Natl. Acad. Sci. USA. 1995, 92, 4725-4727.

  • Lemere, C.A.; Lopera, F.; Kosik, K.S.; Lendon, C.L.; Ossa, J.; Saido, T.C.; Yamaguchi, H.; Ruiz, A.; Martinez, A.; Madrigal, L.; Hincapie, L.; Arango, J.C.; Anthony, D.C.; Koo, E.H.; Goate, A.M.; Selkoe, D.J.; Arango, J.C. Nat Med. 1996, 2,1146-50.

  • Ratovitski, T.; Slunt, H.H.; Thinakaran, G.; Price, D.L.; Sisodia, S.S.; Borchelt, D.R. J. Biol. Chem. 1997, 272, 24536-24541.

  • Edbauer, D.; Winkler,E.; Regula, JT.; Pesold, B.; Steiner H.; Haass, C. Nature Cell Biology. 2003, 5, 486-488.

  • Wolfe, M.S.; Xia, W.; Ostaszewski, B.L.; Diehl, T.S.; Kimberly, W.T.; Selkoe, D.J. Nature. 1999, 398, 513-7.

  • De Strooper, B.; Saftig, P.; Craessaerts, K.; Vanderstichele, H.; Gundula, G.; Annaert, W.; Von Figura, K.; Van Leuven, F. Nature. 1998, 391, 387-390.

  • Edbauer D, Winkler E, Regula JT, Pesold B, et al. Reconstitution of gamma secretase activity. Nat Cell Biol 2003; 5 (5): 486-8.

  • Roberson, E.D.; Mucke, L. Science. 2006, 314, 781-784.

  • Struhl G.; Adachi, A. Molecular Cell. 2000, 6, 625-636.

  • Wong, G.T.; Manfra, D.; Poulet, F.M.; Zhang, G.; Josien, H.; Bara, T.; Engstrom, L.; Pinzon-Ortiz, M.; Fine, J.S.; Lee, H.J.J.; Zhang, L.; Higgins, G.A.; Parker, E.M. J. Biol. Chem, 2004 279, 12876-12882.

  • Beher, D.; Clarke, E.E.; Wrigley, J.D.J.; Martin, A.C.L.; Nadin, A.; Churcher, I.; Shearman, M.S.; J. Biol. Chem. 2004, 279, 43419-43426.

  • Leo, A., Berezovska, O., Herl, L., Raju, S., Deng A., Bacskai BJ., Frosch, MP., Irizary M., Hyman BT. Nature Medicine. 2004, 10, 1065-1066.


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  • Biochemical Origins of Alzheimer's Disease with Treatment Techniques

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Authors

Chirag K. Patel
Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, India
B. Panigrahi
Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, India
R. Badmanaban
Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, India
C. N. Patel
Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, India

Abstract


Alzheimer's disease (AD) is a neurodegenerative disease caused by irregular protein formations in the brain leading to neuronal loss and ultimately affecting the patient's cognitive ability and memory. AD affects nearly 4.5 million Americans, and this number is expected to continue to rise. The pathological manifestations of AD occur in the neurons and are two-fold; the primary cause is the accumulation. β-amyloid (amyloid precursor protein) depositions, which aggregate into pathogenic plaques. The second is the accumulation of paired helical filaments that form into neurofibrillary tangles (NFTs). Amyloid precursor protein plaques result from the sequential cleavage of the amyloid precursor protein (APP) by β-secretase and γ-secretase. NFTs result from the hyperphosphorylation of tau, a stabilizing component of microtubules. Based on current understanding of the Amyloid precursor protein pathway, two major strategies will be discussed that aim at decreasing the deposition of Amyloid precursor protein plaques in the brain. In the first approach, non-streroidal anti-inflammatory drugs alter the APP cleavage site by β-secretase to produce less amyoidogenic plaques. A second method aims at inhibiting γ-secretase activity on APP through allosteric inhibition of ATP binding.

References