| First Author | Wright S | Year | 2012 |
| Journal | Neurobiol Aging | Volume | 33 |
| Issue | 7 | Pages | 1379-88 |
| PubMed ID | 21126803 | Mgi Jnum | J:243536 |
| Mgi Id | MGI:5908788 | Doi | 10.1016/j.neurobiolaging.2010.10.018 |
| Citation | Wright S, et al. (2012) Perlecan domain V inhibits alpha2 integrin-mediated amyloid-beta neurotoxicity. Neurobiol Aging 33(7):1379-88 |
| abstractText | Amyloid-beta (Abeta) peptide is a key component of amyloid plaques, one of the pathological features of Alzheimer's disease. Another feature is pronounced cell loss in the brain leading to an enlargement of the ventricular area and a decrease in brain weight and volume. Abeta plaque deposition and neuronal toxicity can be modeled by treating human cortical neuronal cultures with Abeta and showing robust Abeta deposition and neurotoxicity that is mediated by alpha2beta1 and alphavbeta1 integrins. The current study expands on these findings by showing that the domain V of perlecan, a known alpha2 integrin ligand, inhibits Abeta neurotoxicity in an alpha2 integrin-dependent manner. Additionally, Abeta binds more efficiently to cells expressing activated alpha2 integrin. Finally the inhibition of Abeta neurotoxicity with domain V is synergistic with inhibitors of alphav integrin and beta1 integrin. We propose that domain V and potentially other alpha2 integrin ligands could be a new therapeutic approach for inhibiting the Abeta plaque deposition and neurotoxicity observed in Alzheimer's disease. |
