Swedish mutant APP-based BACE1 binding site peptide reduces APP β-cleavage and cerebral Aβ levels in Alzheimer's mice

Scientific Reports

Volumn 5, Issue , 2015, Pages

  Li, Song ^a,b   Hou, Huayan ^a   Mori, Takashi ^c   Sawmiller, Darrell ^a   Smith, Adam ^a   Tian, Jun ^a   Wang, Yanjiang ^d   Giunta, Brian ^a   Sanberg, Paul R ^a   Zhang, Sheqing ^a,e   Tan, Jun ^a  

^a UNIVERSITY OF SOUTH FLORIDA   (United States)

^b DALIAN MEDICAL UNIVERSITY   (China)

^c SAITAMA MEDICAL UNIVERSITY   (Japan)

^d THIRD MILITARY MEDICAL UNIVERSITY   (China)

^e SECOND MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; ASPARTIC PROTEINASE; BACE1 PROTEIN, MOUSE; HYBRID PROTEIN; PEPTIDE; PROTEIN BINDING; SECRETASE;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; ANIMAL; ANIMAL BEHAVIOR; ANTAGONISTS AND INHIBITORS; BINDING SITE; BLOOD BRAIN BARRIER; BRAIN CORTEX; CHEMISTRY; CHO CELL LINE; CRICETULUS; DISEASE MODEL; GENE EXPRESSION; GENETICS; HIPPOCAMPUS; MEMORY; METABOLISM; MOLECULAR GENETICS; MOLECULAR MODEL; MOUSE; MUTATION; PATHOLOGY; PATHOPHYSIOLOGY; PROTEIN CONFORMATION; PROTEIN DEGRADATION;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ACID ENDOPEPTIDASES; BEHAVIOR, ANIMAL; BINDING SITES; BLOOD-BRAIN BARRIER; CEREBRAL CORTEX; CHO CELLS; CRICETULUS; DISEASE MODELS, ANIMAL; GENE EXPRESSION; HIPPOCAMPUS; MEMORY; MICE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION; PEPTIDES; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEOLYSIS; RECOMBINANT FUSION PROTEINS;

EID: 84934900727     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep11322     Document Type: Article

References (51)

1. Selkoe, D. J. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 399, A23-A31 (1999).
2. Sinha, S. & Lieberburg, I. Cellular mechanisms of β-amyloid production and secretion. Proc Natl Acad Sci USA 96, 11049-11053 (1999).
3. Games, D. et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F [3-amyloid precursor protein. Nature 373, 523-527 (1995).
4. Higgins, L. S. & Cordell, B. Transgenic mice and modeling Alzheimer's disease. Rev Neurosci 6, 87-96 (1995).
5. Seifert, D. et al. Presenilin-1 and-2 are molecular targets for γ-secretase inhibitors. J Biol Chem 275, 34086-34091 (2000).
6. Wolfe, M. S. et al Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity. Nature 398, 513-517 (1999).
7. Shen, J. et al Skeletal and CNS defects in Presenilin-1-defcient mice. Cell 89, 629-639 (1997).
8. Wong, P. C. et al Presenilin 1 is required for Notch1 DII1 expression in the paraxial mesoderm. Nature 387, 288-292 (1997).
9. Haass, C. & De Strooper, B. Te presenilins in Alzheimer's disease-proteolysis holds the key. Science 286, 916-919 (1999).
10. Esler, W P. et al Transition-state analogue inhibitors of γ-secretase bind directly to presenilin-1. Nat Cell Biol 2, 428-434 (2000).
11. Haass, C. Take fve-BACE and the γ-secretase quartet conduct Alzheimer's amyloid [3-peptide generation. EMBO J 23, 483-488 (2004).
12. Coric, V. et al. Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol 69, 1430-1440 (2012).
13. Green, R. C. et al. Efect of tarenfurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. JAMA 302, 2557-2564 (2009).
14. Doody, R. S. et al. A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med 369, 341-350 (2013).
15. Schor, N. F. What the halted phase III γ-secretase inhibitor trial may (or may not) be telling us. Ann Neurol 69, 237-239 (2011).
16. Gupta, V. B., Gupta, V. K. & Martins, R. Semagacestat for treatment of Alzheimer's disease. N Engl J Med 369, 1660-1661 (2013).
17. Ohno, M. et al. BACE1 defciency rescues memory defcits and cholinergic dysfunction in a mouse model of Alzheimer's disease. Neuron 41, 27-33 (2004).
18. Cai, H. et al. BACE1 is the major [3-secretase for generation of A[3 peptides by neurons. Nat Neurosci 4, 233-234 (2001).
19. Hong, L. et al. Structure of the protease domain of memapsin 2 ([3-secretase) complexed with inhibitor. Science 290, 150-153 (2000).
20. Zhu, Z. et al. Discovery of cyclic acylguanidines as highly potent and selective [3-site amyloid cleaving enzyme (BACE) inhibitors: part I-inhibitor design and validation. J Med Chem 53, 951-965 (2010).
21. Wyss, D. F. et al. Combining NMR and X-ray crystallography in fragment-based drug discovery: Discovery of highly potent and selective BACE-1 inhibitors. Top Curr Chem 317, 83-114 (2012).
22. Ghosh, A. K. & Osswald, H. L. BACE1 ([3-secretase) inhibitors for the treatment of Alzheimer's disease. Chem Soc Rev 43, 6765-6813 (2014).
23. Oehlrich, D., Prokopcova, H. & Gijsen, H. J. Te evolution of amidine-based brain penetrant BACE1 inhibitors. Bioorg Med Chem Lett 24, 2033-2045 (2014).
24. Evin, G., Lessene, G. & Wilkins, S. BACE inhibitors as potential drugs for the treatment of Alzheimer's disease: focus on bioactivity. Recent Pat CNS Drug Discov 6, 91-106 (2011).
25. Probst, G. & Xu, Y. Z. Small-molecule BACE1 inhibitors: a patent literature review (2006-2011). Expert Opin Ter Pat 22, 511-540 (2012).
26. Yan, R. & Vassar, R. Targeting the [3 secretase BACE1 for Alzheimer's disease therapy. Lancet Neurol 13, 319-329 (2014).
27. Luo, Y et al. Mice defcient in BACE1, the Alzheimer's [3-secretase, have normal phenotype and abolished [3-amyloid generation. Nat Neurosci 4, 231-232 (2001).
28. Nishitomi, K. et al. BACE1 inhibition reduces endogenous A[3 and alters APP processing in wild-type mice. J Neuro chem 99, 1555-1563 (2006).
29. Willem, M. et al. Control of peripheral nerve myelination by the [3-secretase BACE1. Science 314, 664-666 (2006).
30. Giacobini, E. & Gold, G. Alzheimer disease therapy-moving from amyloid-[3 to tau. Nat Rev Neurol 9, 677-686 (2013).
31. Rezai-Zadeh, K. et al. Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci 25, 8807-8814 (2005).
32. Modi, V., Lama, D. & Sankararamakrishnan, R. Relationship between helix stability and binding afnities: molecular dynamics simulations of Bf-1/A1-binding pro-apoptotic BH3 peptide helices in explicit solvent. J Biomol Struct Dyn 31, 65-77 (2013).
33. Schwarze, S. R., Ho, A., Vocero-Akbani, A. & Dowdy, S. F. In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 285, 1569-1572 (1999).
34. Cao, G. et al. In vivo delivery of a Bcl-xL fusion protein containing the TAT protein transduction domain protects against ischemic brain injury and neuronal apoptosis. J Neurosci 22, 5423-5431 (2002).
35. Zou, L. L., Ma, J. L., Wang, T., Yang, T. B. & Liu, C. B. Cell-penetrating peptide-mediated therapeutic molecule delivery into the central nervous system. Curr Neuropharmacol 11, 197-208 (2013).
36. Azzarito, V., Long, K., Murphy, N. S. & Wilson, A. J. Inhibition of a-helix-mediated protein-protein interactions using designed molecules. Nat Chem 5, 161-173 (2013).
37. Rao, T. et al. Truncated and helix-constrained peptides with high afnity and specifcity for the cFos coiled-coil of AP-1. PLoS ONE 8, e59415 (2013).
38. Oakley, H. et al. Intraneuronal [3-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with fve familial Alzheimer's disease mutations: potential factors in amyloid plaque formation. J Neurosci 26, 10129-10140 (2006).
39. Lin, X. et al. Human aspartic protease memapsin 2 cleaves the [3-secretase site of [3-amyloid precursor protein. Proc Natl Acad Sci USA 97, 1456-1460 (2000).
40. Vassar, R. et al. [3-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735-741 (1999).
41. Hussain, I. et al. Identifcation of a novel aspartic protease (Asp 2) as [3-secretase. Mol Cell Neurosci 14, 419-427 (1999).
42. Obregon, D. et al. Soluble amyloid precursor protein-a modulates [3-secretase activity and amyloid-[3 generation. Nat Commun 3, 777 (2012).
43. Wong, H. K. et al. [3 Subunits of voltage-gated sodium channels are novel substrates of [3-site amyloid precursor protein-cleaving enzyme (BACE1) and γ-secretase. J Biol Chem 280, 23009-23017 (2005).
44. Hu, X. et al. Bace1 modulates myelination in the central and peripheral nervous system. Nat Neurosci 9, 1520-1525 (2006).
45. Tung, J. S. et al. Design of substrate-based inhibitors of human [3-secretase. J Med Chem 45, 259-262 (2002).
46. Cooper, I. et al. Peptide derived from HIV-1 TAT protein destabilizes a monolayer of endothelial cells in an in vitro model of the blood-brain barrier and allows permeation of high molecular weight proteins. J Biol Chem 287, 44676-44683 (2012).
47. Haass, C. et al. Te Swedish mutation causes early-onset Alzheimer's disease by [3-secretase cleavage within the secretory pathway. Nat Med 1, 1291-1296 (1995).
48. Tinakaran, G., Teplow, D. B., Siman, R., Greenberg, B. & Sisodia, S. S. Metabolism of the "Swedish" amyloid precursor protein variant in neuro2a (N2a) cells. Evidence that cleavage at the "[3-secretase" site occurs in the golgi apparatus. J Biol Chem 271, 9390-9397 (1996).
49. Alamed, J., Wilcock, D. M., Diamond, D. M., Gordon, M. N. & Morgan, D. Two-day radial-arm water maze learning and memory task; robust resolution of amyloid-related memory defcits in transgenic mice. Nat Protoc 1, 1671-1679 (2006).
50. Franklin, K. B. J. & Paxinos, G. Te Mouse Brain in Stereotaxic Coordinates, Academic Press, San Diego (2001).
51. Zhu, Y. et al. CD45 defciency drives amyloid-β peptide oligomers and neuronal loss in Alzheimer's disease mice. J Neurosci 31, 1355-1365 (2011).