The physiological metabolism of proteins guarantees that different cellular
compartments contain the appropriate concentration of proteins to perform
their biological functions and, after a variable period of wear and tear, m
ediates their natural catabolism. The equilibrium between protein synthesis
and catabolism ensures an effective turnover, but hereditary or acquired a
bnormalities of protein structure can provoke a premature loss of biologica
l function, an accelerated catabolism and diseases caused by the loss of an
irreplaceable function. In certain proteins, abnormal structure and metabo
lism are associated with a strong tendency to self-aggregation into a polym
eric fibrillar structure, and in these cases the disease is not principally
caused by the loss of an irreplaceable function but by the action of this
new biological entity. Amyloid fibrils are an apparently inert, insoluble,
mainly extracellular protein polymer that kills the cell without tissue nec
rosis but by activation of the apoptotic mechanism. We analyzed the data re
ported so far on the structural and functional properties of four prototypi
c proteins with well-known biological functions (lysozyme, transthyretin, b
eta(2)-microglobulin and apolipoprotein AI) that are able to create amyloid
fibrils under certain conditions, with the perspective of evaluating wheth
er the achievement of biological function favors or inhibits the process of
fibril formation. Furthermore, studying the biological functions carried o
ut by amyloid fibrils reveals new types of protein-protein interactions in
the transmission of messages to cells and may provide new for effective the
rapeutic strategies.