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Amyloid-beta reduction by memapsin 2 (beta-secretase) immunization.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Chang, W. Downs, Deborah Huang, X. Da, Huining Fung, K. M. Tang, Jordan |
| Copyright Year | 2007 |
| Abstract | Memapsin 2 (beta-secretase, BACE1) is the protease that initiates cleavage of beta-amyloid precursor protein leading to the production of amyloid-beta (Abeta) and the onset of Alzheimer's disease (AD). Reducing Abeta by targeting memapsin 2 is a major strategy in developing new AD therapy. Here, in a proof-of-concept study, we show that immunization of transgenic AD mice (Tg2576) with memapsin 2 resulted in Abeta reduction and cognitive improvement. To study the basis of this therapy, we demonstrated that anti-memapsin 2 (anti-M2) antibodies were rapidly internalized and reduced Abeta production in cultured cells. These antibodies also effectively crossed the blood-brain barrier to reach the brain. Two- and 10-month Tg2576 mice were immunized and monitored over 10 and 6 months, respectively. We observed a significant decrease of plasma and brain Abeta40 and Abeta42 (approximately 35%) in the immunized mice as compared to controls. Immunized mice also showed better cognitive performance than controls in both cohorts. Brain histological analyses found no evidence of T cell/microglia/astrocyte activation in the immunized mice, suggesting the absence of inflammatory responses. These results suggest that memapsin 2 immunization in Tg2576 was effective in reducing Abeta production and improving cognitive function and that the current approach warrants further investigation as a therapy for AD. |
| Starting Page | 387 |
| Ending Page | 389 |
| Page Count | 3 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://pdfs.semanticscholar.org/5ca9/863c06f586a9ca2832adedc4507615b4bbc2.pdf |
| Alternate Webpage(s) | http://www.fasebj.org/content/21/12/3184.full.pdf |
| PubMed reference number | 17494994v1 |
| Volume Number | 21 |
| Issue Number | 12 |
| Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Alzheimer's Disease Amyloid beta-Protein Precursor Astrocytes BACE1 gene BACE1 protein, human Blood - brain barrier anatomy Endopeptidases Leukemia, B-Cell Microglia astrocyte activation beta Thalassemia cellular targeting inflammatory response secretase |
| Content Type | Text |
| Resource Type | Article |
