Binding of proteases to fibrillar amyloid protein and its inhibition by Congo red are identified

15 November 2007

Staten Island, NY—Scientists from the New York State Institute for Basic Research in Developmental Disabilities (IBR) report today in the November issue of the Journal of Alzheimer’s Disease that the proteases neprilysin and insulysin bind to fibrillar amyloid beta-protein (fAβ), resulting in the proteases losing their function of helping break down and clear Aβ from cells. With the loss of this function, Aβ accumulates in the brain. fAβ is the main component of amyloid plaques in the brains of individuals with Alzheimer’s disease; proteases are enzymes that can break proteins such as Aβ down into their component peptides.

These findings suggest that the identification of compounds that inhibit the binding of proteases to fAβ would be of therapeutic significance in Alzheimer’s disease. The IBR research team observed that Congo red, a dye used as a biological stain in examination of tissue sections for the presence of amyloid deposits, interferes with the binding of neprilysin and insulysin to fibrillar Aβ, thereby preventing Aβ accumulation. “However, Congo red has toxic properties,” explains lead author Ved Chauhan, head of IBR’s Cellular Neurochemistry Laboratory. “Therefore, we are working now to identify agents similar to Congo red that are not toxic and can interfere with the binding of proteases to fAβ.” Once those agents are identified, the researchers will perform experiments in an animal model of Alzheimer’s disease to determine the effectiveness of the agents in inhibiting binding of proteases to fAβ.

These findings were published in the Journal of Alzheimer’s Disease 2007; 12(3).

Contact: Maureen Marlow