β-Secretase (BACE1) Purification by Refolding Method and Complex with Hispidin
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Alzheimer’s disease (AD) is a devastating neurodegenerative disease that represents the most common form of dementia among the elderly population. The deposition of aggregated β-amyloid (Aβ) senile plaques in the human brain is a classic observation in the neuropathology of AD, yet an understanding of the mechanism of their formation remains elusive. Aβ is formed through endoproteolysis of the amyloid precursor protein (APP) by β-secretase (BACE1, β-site APP-cleaving enzyme) and γ-secretase. In this study, BACE1 protein was successfully over-expressed, purified, and refolded and utilized in a binding study with hispidin. We developed a simpler refolding method using a urea gradient and size-exclusion gel filtration to purify an active BACE1 protein variant, in larger quantities than that reported previously, and measured the binding affinity of hispidin to the BACE1 protein variant through isothermal titration calorimetry.
Abstract
Alzheimer’s disease (AD) is a devastating neurodegenerative disease that represents the most common form of dementia among the elderly population. The deposition of aggregated β-amyloid (Aβ) senile plaques in the human brain is a classic observation in the neuropathology of AD, yet an understanding of the mechanism of their formation remains elusive. Aβ is formed through endoproteolysis of the amyloid precursor protein (APP) by β-secretase (BACE1, β-site APP-cleaving enzyme) and γ-secretase. In this study, BACE1 protein was successfully over-expressed, purified, and refolded and utilized in a binding study with hispidin. We developed a simpler refolding method using a urea gradient and size-exclusion gel filtration to purify an active BACE1 protein variant, in larger quantities than that reported previously, and measured the binding affinity of hispidin to the BACE1 protein variant through isothermal titration calorimetry.
참고문헌 (32)
- Herrmann, N, , Drugs, 71, pp.2031~2065 (2011)
- de la Torre, J. C, , J. Alzheimers Dis, 4, pp.497~512 (2002)
- Kalaria, R. N, , Lancet. Neurol, 7, pp.812~826 (2008)
- Weidner, A. M, , Plos. One, 6 (2011)
- Wozniak, M. A, , Plos. One, 6 (2011)
- Tanahashi, H, , Neuroscience Letters, 307, pp.9~12 (2001)
- Glenner, G. G, , Biochem. Biophys. Res. Commun, 120, pp.885~890 (1984)
- Hardy, J, , Trends Pharmacol Sci, 12, pp.383~388 (1991)
- Harun, A, , BMC Complement Altern Med, 11, pp.79~ (2011)
- Sinha, S, , Nature, 402, pp.537~540 (1999)
- Mileusnic, R, , Ann. N.Y. Acad. Sci, 1048, pp.149~165 (2005)
- Robakis, N. K, , Proc. Natl. Acad. Sci, 84, pp.4190~4194 (1987)
- Tanzi, R. E, , Bertram, L. Cell, 120, pp.545~555 (2005)
- Sinha, S, , Proceedings of the National Academy of Sciences of the United States of America, 96, pp.11049~11053 (1999)
- Esch, F. S, , J. Science, 248, pp.1122~1124 (1990)
- Sardana, V, , Protein. Expr. Purif, 34, pp.190~196 (2004)
- Selkoe, D, , J. Physiol. Rev, 81, pp.741~766 (2001)
- Hardy, J, , J. Science, 297, pp.353~356 (2002)
- Bruinzeel, W, , Protein. Expres. Purif, 26, pp.139~148 (2002)
- Jang, J. S, , Arch. Pharm. Res, 33, pp.853~861
- Gonindard, C, , Cell. Biol. Toxicol, 13, pp.141~153 (1997)
- Park, I. H, , Arch. Pharm. Res, 27, pp.615~618 (2004)
- Ali, N. A. A, , Fitoterapia, 74, pp.483~485 (2003)
- Bachman, D. L, , Neurology, 43, pp.515~519 (1993)
- Tamagno, E, , Neurotoxicity Research, 22, pp.208~219 (2012)
- Lorenzo, A, , Nat. Neurosci, 3, pp.460~464 (2000)
- Dodart, J. C, , Nature Neuroscience, 5, pp.452~457 (2002)
- Lesne, S, , Nature, 440, pp.352~357 (2006)
- Selkoe, D. J, , Ann. N. Y. Acad. Sci, 924, pp.17~25 (2000)
- Sorribas, A, , Bioorganic & Medicinal Chemistry, 19, pp.6581~6586 (2011)
- Alibolandi, M, , Afr. J. Biotechnol, 9, pp.2456~2462 (2010)
- Hong, L, , Tang, J. Science, 290, pp.150~153 (2000)