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Developing a novel peptide aptamer‐based treatment of Alzheimer’s disease
Author(s) -
Ali Tahir,
Klein Antonia N.,
Vu Alex,
Gilch Sabine
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.056115
Subject(s) - in vitro , neurotoxicity , in vivo , genetically modified mouse , mtt assay , aptamer , pharmacology , toxicity , psen1 , transgene , amyloid (mycology) , chemistry , microbiology and biotechnology , alzheimer's disease , presenilin , medicine , biology , disease , biochemistry , pathology , gene
Background Alzheimer’s disease (AD) is a major cause of dementia and age‐related neurodegenerative disease with no current treatment. Pathologically, AD is characterized primarily by accumulation of amyloid‐β (Aβ) in the brain. The interaction of Aβ‐oligomers (Aβo) with the cellular prion protein (PrP C ) subsequently mediated AD pathologies. The interference with Aβo‐PrP C interaction is a valuable strategy for developing therapeutics for AD. Previously, we developed peptide aptamers (PAs) binding to the PrP C , partially covering the binding site of Aβo . In this study, we aimed to investigate the PAs effects on preventing Aβo‐PrP C interaction and toxicity in vitro and pathologies in AD models. Method Wild type mouse neuroblastoma N2a cells (overexpressing mouse PrP) were treated with Aβ (1 mM) and PAs (10 µg/ml), and after 24 hr performed the MTT assay. Following these in vitro experiments, we carried out in vivo experiments using transgenic 5xFAD (expressing human APP and PSEN1 transgenes harboring in total 5 mutations associated with familial AD) mice. The 5xFAD mice were treated with PAs at a 14.4 ug /day dosage for 6 weeks by intraventricular infusion using Alzet® osmotic pumps. After completion of treatment, fear conditioning test (FCT) was performed for consolidated leaning and memory functions of the 5xFAD mice. Result The MTT results indicated that PA treatment significantly reduced Aβo‐induced toxicity. Overall, our in vitro results indicated that PAs reduced Aβ‐induced neurotoxicity. In the FCT, we observed that PAs increased the time of freezing percentage as comparted to the non‐treated 5xFAD mice. The FCT results represented that PAs significantly improved consolidated learning and memory functions of 5xFAD mice as compared to the non‐treated 5xFAD mice. Conclusion Our results demonstrate that treatment with PAs targeting Aβo‐PrP C interaction would be valuable and novel strategy to treat AD.