| First Author | Wang J | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8876 | PubMed ID | 26581893 |
| Mgi Jnum | J:228025 | Mgi Id | MGI:5704271 |
| Doi | 10.1038/ncomms9876 | Citation | Wang J, et al. (2015) TRPC6 specifically interacts with APP to inhibit its cleavage by gamma-secretase and reduce Abeta production. Nat Commun 6:8876 |
| abstractText | Generation of beta-amyloid (Abeta) peptide in Alzheimer's disease involves cleavage of amyloid precursor protein (APP) by gamma-secretase, a protease known to cleave several substrates, including Notch. Finding specific modulators for gamma-secretase could be a potential avenue to treat the disease. Here, we report that transient receptor potential canonical (TRPC) 6 specifically interacts with APP leading to inhibition of its cleavage by gamma-secretase and reduction in Abeta production. TRPC6 interacts with APP (C99), but not with Notch, and prevents C99 interaction with presenilin 1 (PS1). A fusion peptide derived from TRPC6 also reduces Abeta levels without effect on Notch cleavage. Crossing APP/PS1 mice with TRPC6 transgenic mice leads to a marked reduction in both plaque load and Abeta levels, and improvement in structural and behavioural impairment. Thus, TRPC6 specifically modulates gamma-secretase cleavage of APP and preventing APP (C99) interaction with PS1 via TRPC6 could be a novel strategy to reduce Abeta formation. |
