In vivo inhibition of Aβ production by memapsin 2 (β-secretase) inhibitors

Journal of Neurochemistry

Volumn 89, Issue 6, 2004, Pages 1409-1416

  Chang, Wan Pin ^a   Koelsch, Gerald ^a,b   Wong, Stephen ^c   Downs, Deborah ^a   Da, Huining ^a   Weerasena, Vajira ^a,b   Gordon, Brian ^a   Devasamudram, Thippeswamy ^a   Bilcer, Geoffrey ^b   Ghosh, Arun K ^d   Tang, Jordan ^a,c  

^a OKLAHOMA MEDICAL RESEARCH FOUNDATION   (United States)

^b Zapaq Inc   (United States)

^c UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

^d UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

secretase; Alzheimer's disease; Amyloid ; Inhibition; Mouse model

Indexed keywords

AMYLOID BETA PROTEIN; BETA SECRETASE; BETA SECRETASE INHIBITOR; CARRIER PEPTIDE; CARRIER PROTEIN; OM00 3; OM99 2; PEPTIDE; UNCLASSIFIED DRUG; AMYLOID BETA PROTEIN[1-40]; ASPARTIC PROTEINASE; BACE1 PROTEIN, HUMAN; BACE1 PROTEIN, MOUSE; DRUG CARRIER; DRUG DERIVATIVE; ENZYME INHIBITOR; FLUORESCEIN ISOTHIOCYANATE; FS(OM00 3)DR9 PEPTIDE; FS(OM00-3)DR9 PEPTIDE; FS(OM99 2)TAT PEPTIDE; FS(OM99-2)TAT PEPTIDE; OLIGOPEPTIDE; PEPTIDE FRAGMENT; PROTEINASE; SECRETASE;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD BRAIN BARRIER; CONTROLLED STUDY; DRUG CONJUGATION; DRUG MECHANISM; DRUG PENETRATION; DRUG TARGETING; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; TRANSGENIC MOUSE; ANIMAL; BLOOD; BRAIN; CELL LINE; CELL MEMBRANE; CHEMISTRY; DISEASE MODEL; DOSE RESPONSE; DRUG ANTAGONISM; DRUG EFFECT; DRUG SCREENING; INTRAPERITONEAL DRUG ADMINISTRATION; METABOLISM; PHYSIOLOGY;

ANIMALIA; MUS MUSCULUS;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ENDOPEPTIDASES; BLOOD-BRAIN BARRIER; BRAIN; CELL LINE; CELL MEMBRANE; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG CARRIERS; DRUG EVALUATION, PRECLINICAL; ENDOPEPTIDASES; ENZYME INHIBITORS; FLUORESCEIN-5-ISOTHIOCYANATE; HUMANS; INJECTIONS, INTRAPERITONEAL; MICE; MICE, TRANSGENIC; OLIGOPEPTIDES; PEPTIDE FRAGMENTS; PEPTIDES;

EID: 3042658599     PISSN: 00223042     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1471-4159.2004.02452.x     Document Type: Article

References (27)

1. Cai H., Wang Y., McCarthy D., Wen H., Borchelt D. R., Price D. L. and Wong P. C. (2001) BACE1 is the major β-secretase for generation of Aβ peptides by neurons. Nat. Neurosci. 4, 233-234.
2. DeMattos R. B., Bales K. R., Cummins D. J., Dodart J. C., Paul S. M. and Holtzman D. M. (2001) Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease. Proc. Natl Acad. Sci. USA 98, 8850-8855.
3. DeMattos R. B., Bales K. R., Cummins D. J., Paul S. M. and Holtzman D. M. (2002) Brain to plasma amyloid-β efflux: a measure of brain amyloid burden in mouse model of Alzheimer's disease. Science 295, 2264-2267.
4. Dodart J. C., Bales K. R., Gannon K. S. et al. (2002) Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model. Nat. Neurosci. 5, 452-457.
5. Dominguez D. I. and De Strooper B. (2002) Novel therapeutic strategies provide the real test for the amyloid hypothesis of Alzheimer's disease. Trends Pharmacol. Sci. 23, 324-330.
6. Ermolieff J., Loy J. A., Koelsch G. and Tang J. (2000) Proteolytic activation of recombinant pro-memapsin 2 (pro-β-secretase) studied with new fluorogenic substrates. Biochemistry 39, 12450-12456.
7. Fawell S., Seery J., Daikh Y., Moore C., Chen L. L., Pepinsky B. and Barsoum J. (1994) Tat-mediated delivery of heterologous proteins into cells. Proc. Natl Acad. Sci. USA 91, 664-668.
8. Ghosh A. K., Shin D., Downs D., Koelsch G., Lin X., Ermolieff J. and Tang J. (2000) Design of potent inhibitors for human brain memapsin 2 (β-secretase). J. Am. Chem. Soc. 122, 3522-3523.
9. Ghosh A. K., Bilcer G., Harwood C. et al. (2001) Structure-based design: potent inhibitors of human brain memapsin 2 (β-secretase). J. Med. Chem. 44, 2865-2868.
10. Ghosh A. K., Hong L. and Tang J. (2002) β-Secretase as a therapeutic target for inhibitor drugs. Curr. Med. Chem. 9, 1135-1144.
11. Hsiao K., Chapman P., Nilsen S., Eckman C., Harigaya Y., Younkin S., Yang F. and Cole G. (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274, 99-102.
12. Hussain I., Powell D., Howlett D. R. et al. (1999) Identification of a novel aspartic protease (Asp 2) as β-secretase. Mol. Cell. Neurosci. 14, 419-427.
13. Johnson-Wood K., Lee M., Motter R. et al. (1997) Amyloid precursor protein processing and Aβ42 deposition in a transgenic mouse-model of Alzheimer disease. Proc. Natl Acad. Sci. USA 94, 1550-1555.
14. Kawarabayashi T., Younkin L. H., Saido T. C., Shoji M., Ashe K. H. and Younkin S. G. (2001) Age-dependent changes in brain, CSF, and plasma amyloid β protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J. Neurosci. 21, 372-381.
15. Lin X., Lin X., Koelsch G., Wu S., Downs D., Dashti A. and Tang J. (2000) Human aspartic protease memapsin 2 cleaves the β-secretase site of β-amyloid precursor protein. Proc. Natl Acad. Sci. USA 97, 1456-1460.
16. Luo Y., Bolon B., Kahn S. et al. (2001) Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation. Nat. Neurosci. 4, 231-232.
17. Morgan D., Diamond D. M., Gottschall P. E. et al. (2000) Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408, 982-985.
18. Phiel C. J., Wilson C. A., Lee V. M. and Klein P. S. (2003) GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides. Nature 423, 435-439.
19. Roberds S. L., Anderson J., Basi G. et al. (2001) BACE knockout mice are healthy despite lacking the primary β-secretase activity in brain: implications for Alzheimer's disease therapeutics. Hum. Mol. Genet. 10, 1317-1324.
20. Schwarze S. R., Ho A., Vocero-Akbani A. and Dowdy S. F. (1999) In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 285, 1569-1572.
21. Selkoe D. J. (1999) Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 399A, 23-31.
22. Sinha S., Anderson J. P., Barbour R. et al. (1999) Purification and cloning of amyloid precursor protein β-secretase from human brain. Nature 402, 537-540.
23. Turner R. T. III, Koelsch G., Hong L., Castanheira P., Ermolieff J., Ghosh A. K. and Tang J. (2001) Subsite specificity of memapsin 2 (β-secretase): implications for inhibitor design. Biochemistry 40, 10001-10006.
24. Vassar R., Bennett B. D., Babu-Khan S. et al. (1999) β-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735-741.
25. Walsh D. M., Klyubin I., Fadeeva J. V., Cullen W. K., Anwyl R., Wolfe M. S., Rowan M. J. and Selkoe D. J. (2002) Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535-539.
26. Wender P. A., Mitchell D. J., Pattabiraman K., Pelkey E. T., Steinman L. and Rothbard J. B. (2000) The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: peptoid molecular transporters. Proc. Natl Acad. Sci. USA 97, 13003-13008.
27. Yan R., Bienkowski M. J., Shuck M. E. et al. (1999) Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity. Nature 402, 533-537.