Abstract | BACKGROUND: Central to the pathogenesis of Alzheimer's disease (AD) and many other neurodegenerative diseases is the conformational change of a normal self- protein into toxic oligomeric species and amyloid deposits. None of these disorders have an effective therapy, but immunization approaches hold great promise. We have previously shown that active immunization with a novel peptide when polymerized into a stable oligomeric conformation, pBri, induced a humoral immune response to toxic Aβ species in an AD model, APP/PS1 transgenic (Tg) mice, reducing plaque deposits. pBri is a glutaraldehyde polymerized form of the carboxyl fragment of an amyloidogenic protein, which is deposited in the brains of patients with a rare autosomal dominant disease due to a missense mutation in a stop codon, resulting in the translation of an intronic sequence, with no known sequence homology to any mammalian protein. METHODS: RESULTS: Our results indicate that this immunomodulation approach, which produces a humoral response to proteins in a pathological conformation, is effective at reducing both Aβ and tau-related pathologies. CONCLUSIONS: This immunomodulatory approach has the advantage of using a non-self-immunogen that is less likely to be associated with autoimmune toxicity. Furthermore we found that it is able to target all the cardinal features of AD concurrently.
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Authors | Fernando Goñi, Krystal Herline, Daniel Peyser, Kinlung Wong, Yong Ji, Yanjie Sun, Pankaj Mehta, Thomas Wisniewski |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 10
Pg. 150
(Dec 13 2013)
ISSN: 1742-2094 [Electronic] England |
PMID | 24330773
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amyloid beta-Peptides
- Amyloidogenic Proteins
- tau Proteins
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Topics |
- Alzheimer Disease
(immunology, pathology)
- Amyloid beta-Peptides
(immunology)
- Amyloidogenic Proteins
(chemistry, immunology)
- Animals
- Blotting, Western
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Humans
- Immunization
- Luminescent Measurements
- Mice
- Mice, Transgenic
- Molecular Mimicry
- Protein Structure, Secondary
- tau Proteins
(immunology)
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