QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (129) Citing Articles via Google Scholar Google Scholar Articles by Marr, R. A. Articles by Masliah, E. Search for Related Content PubMed PubMed Citation Articles by Marr, R. A. Articles by Masliah, E.

 Previous Article  |  Next Article 

The Journal of Neuroscience, March 15, 2003, 23(6):1992

BRIEF COMMUNICATION
Neprilysin Gene Transfer Reduces Human Amyloid Pathology in Transgenic Mice

Robert A. Marr¹, Edward Rockenstein², Atish Mukherjee⁴, Mark S. Kindy⁵, Louis B. Hersh⁴, Fred H. Gage¹, Inder M. Verma¹, and Eliezer Masliah^{2, 3}

¹ Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, Departments of ² Neurosciences and ³ Pathology, The University of California San Diego, La Jolla, California 92093, and ⁴ Department of Biochemistry, The University of Kentucky, Lexington, Kentucky 40536, and ⁵ Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, SC 29425

The degenerative process of Alzheimer's disease is linked to a shift in the balance between amyloid- (A) production, clearance, and degradation. Neprilysin has recently been implicated as a major extracellular A degrading enzyme in the brain. However, there has been no direct demonstration that neprilysin antagonizes the deposition of amyloid- in vivo. To address this issue, a lentiviral vector expressing human neprilysin (Lenti-Nep) was tested in transgenic mouse models of amyloidosis. We show that unilateral intracerebral injection of Lenti-Nep reduced amyloid- deposits by half relative to the untreated side. Furthermore, Lenti-Nep ameliorated neurodegenerative alterations in the frontal cortex and hippocampus of these transgenic mice. These data further support a role for neprilysin in regulating cerebral amyloid deposition and suggest that gene transfer approaches might have potential for the development of alternative therapies for Alzheimer's disease.

Key words: neprilysin; Alzheimer's disease; lentivirus; gene therapy; amyloid-; endopeptidase

---

Copyright © 2003 Society for Neuroscience  0270-6474/03/2361992-05$05.00/0

This article has been cited by other articles:

				B. Spencer, R. Potkar, M. Trejo, E. Rockenstein, C. Patrick, R. Gindi, A. Adame, T. Wyss-Coray, and E. Masliah Beclin 1 Gene Transfer Activates Autophagy and Ameliorates the Neurodegenerative Pathology in {alpha}-Synuclein Models of Parkinson's and Lewy Body Diseases J. Neurosci., October 28, 2009; 29(43): 13578 - 13588. [Abstract] [Full Text] [PDF]

				W. J. Meilandt, M. Cisse, K. Ho, T. Wu, L. A. Esposito, K. Scearce-Levie, I. H. Cheng, G.-Q. Yu, and L. Mucke Neprilysin Overexpression Inhibits Plaque Formation But Fails to Reduce Pathogenic A{beta} Oligomers and Associated Cognitive Deficits in Human Amyloid Precursor Protein Transgenic Mice J. Neurosci., February 18, 2009; 29(7): 1977 - 1986. [Abstract] [Full Text] [PDF]

				J. B. Rose, L. Crews, E. Rockenstein, A. Adame, M. Mante, L. B. Hersh, F. H. Gage, B. Spencer, R. Potkar, R. A. Marr, et al. Neuropeptide Y Fragments Derived from Neprilysin Processing Are Neuroprotective in a Transgenic Model of Alzheimer's Disease J. Neurosci., January 28, 2009; 29(4): 1115 - 1125. [Abstract] [Full Text] [PDF]

				W.-h. Wu, P. Lei, Q. Liu, J. Hu, A. P. Gunn, M.-s. Chen, Y.-f. Rui, X.-y. Su, Z.-p. Xie, Y.-F. Zhao, et al. Sequestration of Copper from {beta}-Amyloid Promotes Selective Lysis by Cyclen-Hybrid Cleavage Agents J. Biol. Chem., November 14, 2008; 283(46): 31657 - 31664. [Abstract] [Full Text] [PDF]

				K. Iijima-Ando, S. A. Hearn, L. Granger, C. Shenton, A. Gatt, H.-C. Chiang, I. Hakker, Y. Zhong, and K. Iijima Overexpression of Neprilysin Reduces Alzheimer Amyloid-{beta}42 (A{beta}42)-induced Neuron Loss and Intraneuronal A{beta}42 Deposits but Causes a Reduction in cAMP-responsive Element-binding Protein-mediated Transcription, Age-dependent Axon Pathology, and Premature Death in Drosophila J. Biol. Chem., July 4, 2008; 283(27): 19066 - 19076. [Abstract] [Full Text] [PDF]

				S. S. El-Amouri, H. Zhu, J. Yu, R. Marr, I. M. Verma, and M. S. Kindy Neprilysin: An Enzyme Candidate to Slow the Progression of Alzheimer's Disease Am. J. Pathol., May 1, 2008; 172(5): 1342 - 1354. [Abstract] [Full Text] [PDF]

				L. Crews, H. Mizuno, P. Desplats, E. Rockenstein, A. Adame, C. Patrick, B. Winner, J. Winkler, and E. Masliah {alpha}-Synuclein Alters Notch-1 Expression and Neurogenesis in Mouse Embryonic Stem Cells and in the Hippocampus of Transgenic Mice J. Neurosci., April 16, 2008; 28(16): 4250 - 4260. [Abstract] [Full Text] [PDF]

				K. Kawahara, M. Hashimoto, P. Bar-On, G. J. Ho, L. Crews, H. Mizuno, E. Rockenstein, S. Z. Imam, and E. Masliah {alpha}-Synuclein Aggregates Interfere with Parkin Solubility and Distribution: ROLE IN THE PATHOGENESIS OF PARKINSON DISEASE J. Biol. Chem., March 14, 2008; 283(11): 6979 - 6987. [Abstract] [Full Text] [PDF]

				Y. S. Eisele, M. Baumann, B. Klebl, C. Nordhammer, M. Jucker, and E. Kilger Gleevec Increases Levels of the Amyloid Precursor Protein Intracellular Domain and of the Amyloid-beta degrading Enzyme Neprilysin Mol. Biol. Cell, September 1, 2007; 18(9): 3591 - 3600. [Abstract] [Full Text] [PDF]

				W. Farris, S. G. Schutz, J. R. Cirrito, G. M. Shankar, X. Sun, A. George, M. A. Leissring, D. M. Walsh, W. Q. Qiu, D. M. Holtzman, et al. Loss of Neprilysin Function Promotes Amyloid Plaque Formation and Causes Cerebral Amyloid Angiopathy Am. J. Pathol., July 1, 2007; 171(1): 241 - 251. [Abstract] [Full Text] [PDF]

				S. Zraika, R. L. Hull, J. Udayasankar, A. Clark, K. M. Utzschneider, J. Tong, F. Gerchman, and S. E. Kahn Identification of the Amyloid-Degrading Enzyme Neprilysin in Mouse Islets and Potential Role in Islet Amyloidogenesis Diabetes, February 1, 2007; 56(2): 304 - 310. [Abstract] [Full Text] [PDF]

				E. D. Roberson and L. Mucke 100 Years and Counting: Prospects for Defeating Alzheimer's Disease Science, November 3, 2006; 314(5800): 781 - 784. [Abstract] [Full Text] [PDF]

				K.-J. Yin, J. R. Cirrito, P. Yan, X. Hu, Q. Xiao, X. Pan, R. Bateman, H. Song, F.-F. Hsu, J. Turk, et al. Matrix Metalloproteinases Expressed by Astrocytes Mediate Extracellular Amyloid-beta Peptide Catabolism J. Neurosci., October 25, 2006; 26(43): 10939 - 10948. [Abstract] [Full Text] [PDF]

				S.-M. Huang, A. Mouri, H. Kokubo, R. Nakajima, T. Suemoto, M. Higuchi, M. Staufenbiel, Y. Noda, H. Yamaguchi, T. Nabeshima, et al. Neprilysin-sensitive Synapse-associated Amyloid-beta Peptide Oligomers Impair Neuronal Plasticity and Cognitive Function J. Biol. Chem., June 30, 2006; 281(26): 17941 - 17951. [Abstract] [Full Text] [PDF]

				X. Yue, M. Lu, T. Lancaster, P. Cao, S.-I. Honda, M. Staufenbiel, N. Harada, Z. Zhong, Y. Shen, and R. Li Brain estrogen deficiency accelerates A{beta} plaque formation in an Alzheimer's disease animal model PNAS, December 27, 2005; 102(52): 19198 - 19203. [Abstract] [Full Text] [PDF]

				Q. Li, Q. Lu, G. Estepa, and I. M. Verma Identification of 14-3-3{sigma} mutation causing cutaneous abnormality in repeated-epilation mutant mouse PNAS, November 1, 2005; 102(44): 15977 - 15982. [Abstract] [Full Text] [PDF]

				J.-C. Dodart, R. A. Marr, M. Koistinaho, B. M. Gregersen, S. Malkani, I. M. Verma, and S. M. Paul Gene delivery of human apolipoprotein E alters brain A{beta} burden in a mouse model of Alzheimer's disease PNAS, January 25, 2005; 102(4): 1211 - 1216. [Abstract] [Full Text] [PDF]

				L. Morelli, R. E. Llovera, I. Mathov, L.-F. Lue, B. Frangione, J. Ghiso, and E. M. Castano Insulin-degrading Enzyme in Brain Microvessels: PROTEOLYSIS OF AMYLOID {beta} VASCULOTROPIC VARIANTS AND REDUCED ACTIVITY IN CEREBRAL AMYLOID ANGIOPATHY J. Biol. Chem., December 31, 2004; 279(53): 56004 - 56013. [Abstract] [Full Text] [PDF]

				C. Crozet, Y.-L. Lin, C. Mettling, C. Mourton-Gilles, P. Corbeau, S. Lehmann, and V. Perrier Inhibition of PrPSc formation by lentiviral gene transfer of PrP containing dominant negative mutations J. Cell Sci., November 1, 2004; 117(23): 5591 - 5597. [Abstract] [Full Text] [PDF]

				I. Dolev and D. M. Michaelson A nontransgenic mouse model shows inducible amyloid-{beta} (A{beta}) peptide deposition and elucidates the role of apolipoprotein E in the amyloid cascade PNAS, September 21, 2004; 101(38): 13909 - 13914. [Abstract] [Full Text] [PDF]

				N. Iwata, H. Mizukami, K. Shirotani, Y. Takaki, S.-i. Muramatsu, B. Lu, N. P. Gerard, C. Gerard, K. Ozawa, and T. C. Saido Presynaptic Localization of Neprilysin Contributes to Efficient Clearance of Amyloid-{beta} Peptide in Mouse Brain J. Neurosci., January 28, 2004; 24(4): 991 - 998. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help