Fragmentations of transthyretin in familial amyloid polyneuropathy

2014 Fiscal Year Final Research Report

• Project/Area Number: 25870541
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine; Neurology
• Research Institution: Kumamoto University
• Principal Investigator: UEDA Mitsuharu 熊本大学, 医学部附属病院, 講師 (60452885)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: トランスサイレチン / アミロイドーシス

Outline of Final Research Achievements

Fragmentations of transthyretin (TTR) were reportedly found in amyloid deposits in familial amyloid neuropathy (FAP). However, the mechanism and pathological roles of the TTR fragmentations in FAP remain to be determined. To elucidate the mechanism involved in TTR fragmentations, we investigated how TTR fragments were formed in cultured cells.
Recombinat TTR was employed in this study. Several kinds of cultured cells were incubated for 24 hours with soluble TTR or TTR aggregates formed in vitro by pretreating in an acidic buffer. After incubation, cell lysates were examined by SDS-PAGE and amino-acid sequence analysis to detect TTR fragments. TTR fragments were detected in lysates of neuron (SH-SY5H) and astrocyte (U87MG) cell lines which were incubated with TTR aggregates, but not in those which were incubated with soluble TTR. Amino-acid sequence analysis revealed that cleavages of TTR were made at C-terminal portions.

Free Research Field

神経内科学、アミロイドーシス