BRI2 as a central protein involved in neurodegeneration.

BRI2 is a protein that when mutated causes familial British and familial Danish dementias. Upon cleavage, the mutated BRI2 proteins release the peptides ABri and ADan, which are amyloidogenic and accumulate in the brains of patients. Although BRI2 has an unknown function, several reports indicate that it could play multiple roles. For example, the fact that it exists at the cell surface as a homodimer indicates that it could be involved in cell signaling events by acting as a receptor. BRI2 also interacts with amyloid precursor protein (APP), involved in Alzheimer's disease (AD). In cell cultures and mouse models of AD, BRI2 inhibits APP processing and reduces amyloid beta peptide deposition. The interaction between the two proteins could be responsible for the neuropathological similarities between familial British/Danish dementias and AD. The study of BRI2, which is central in familial British and Danish dementia, could unravel underlying molecular mechanisms of neurodegeneration.