| First Author | Krohn M | Year | 2011 |
| Journal | J Clin Invest | Volume | 121 |
| Issue | 10 | Pages | 3924-31 |
| PubMed ID | 21881209 | Mgi Jnum | J:178230 |
| Mgi Id | MGI:5297739 | Doi | 10.1172/JCI57867 |
| Citation | Krohn M, et al. (2011) Cerebral amyloid-beta proteostasis is regulated by the membrane transport protein ABCC1 in mice. J Clin Invest 121(10):3924-31 |
| abstractText | In Alzheimer disease (AD), the intracerebral accumulation of amyloid-beta (Abeta) peptides is a critical yet poorly understood process. Abeta clearance via the blood-brain barrier is reduced by approximately 30% in AD patients, but the underlying mechanisms remain elusive. ABC transporters have been implicated in the regulation of Abeta levels in the brain. Using a mouse model of AD in which the animals were further genetically modified to lack specific ABC transporters, here we have shown that the transporter ABCC1 has an important role in cerebral Abeta clearance and accumulation. Deficiency of ABCC1 substantially increased cerebral Abeta levels without altering the expression of most enzymes that would favor the production of Abeta from the Abeta precursor protein. In contrast, activation of ABCC1 using thiethylperazine (a drug approved by the FDA to relieve nausea and vomiting) markedly reduced Abeta load in a mouse model of AD expressing ABCC1 but not in such mice lacking ABCC1. Thus, by altering the temporal aggregation profile of Abeta, pharmacological activation of ABC transporters could impede the neurodegenerative cascade that culminates in the dementia of AD. |
