22 October 1999. It is likely that a process very reminiscent of that suggested for Aβ formation-fibrillar protein deposition-is to blame for the rare, inherited disorder Familial British Dementia (FBD), according to a report in the most recent Nature Neuroscience. FBD shares features of Alzheimer's disease, including amyloid deposits, neurofibrillary tangles, neuronal loss, and progressive dementia. The cause of the disease was identified earlier this year as a mutation in a gene termed BRI. The mutant BRI codes for an abnormal protein dubbed ABri, a major component of plaques in FBD.
The structure of ABri suggested that it was cleaved by the prohormone convertase, furin. Sam Sisodia and his colleagues from the University of Chicago and Rockefeller University report that furin constitutively processes both ABri and the normal protein product of BRI with subsequent secretion of carboxyl terminal peptides that encompass all or part of ABri. More significantly, furin generates more peptide product in the presence of the mutant BRI protein and the peptides thus produced assemble into irregular, short fibrils.
Although the role of ABri peptides in the genesis of FBD is not known, it seems likely that the elucidation of this process can shed light on the role of abnormal protein aggregation in other neurodegenerative diseases such as Alzheimer's.-Hakon Heimer.
Reference:Kim SH, Wang R, Gordon DJ, Bass J, Steiner DF, Lynn DG, Thinakaran G, Meredith SC, Sisodia SS. Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia. Nature Neurosci 1999 November;2(11):984-988. Abstract