Arginine: A potential prophylactic supplement for transthyretin amyloidosis

Transthyretin (TTR) is an amyloidogenic protein associated with TTR amyloidosis (ATTR). Dissociation of TTR tetramers into TTR monomers causes TTR misfolding, resulting in amyloid fibril formation and triggering the onset of ATTR. Low-molecular-weight tetrameric TTR stabilizers are potential therapeutic agents to delay ATTR progression. However, the currently available drugs are expensive and cannot be used for prophylaxis. Therefore, in this study, we aimed to identify a prophylactic supplement that suppresses TTR amyloid formation. We investigated whether arginine, an amyloidogenic protein aggregation inhibitor, stabilizes tetrameric TTR, thereby preventing amyloid fibril formation. Immunoblotting showed that arginine mixed with wild-type TTR (TTRwt), amyloidogenic TTR Val30Met (ATTR V30M), and human serum samples reduced the amount of monomeric TTR but increased the tetramer/monomer ratio of TTR compared to those in the samples without arginine. Additionally, oral administration of arginine (5000 mg for 5 days) to healthy volunteers effectively increased the tetramer/monomer ratio of TTR in the serum. Thioflavin T test, a quantitative analysis method for amyloid fibril formation, showed that amyloid fibril formation was significantly suppressed with arginine compared to that without arginine. As arginine is a common supplement and non-toxic amino acid, it can be used as a promising prophylactic supplement to suppress amyloid fibril formation in ATTR.