title: Loss of functional albumin triggers acceleration of transthyretin amyloid fibril formation in familial amyloidotic polyneuropathy.
abstract: Transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) is characterized by systemic accumulation of amyloid fibrils caused by a point mutation in the TTR gene. Despite the urgent need for alternative therapeutic strategies, the pathogenesis of FAP still remains elusive. In our study reported here, we focused on albumin, the most abundant protein in plasma, and described the role of albumin in the TTR amyloid-formation process. Patients with FAP evidenced significantly decreased serum albumin levels as the disease progressed. Biacore analysis showed that albumin had a binding affinity for TTR and exhibited higher affinity for TTR amyloid than native TTR. Albumin functioning as an antioxidant effectively suppressed TTR amyloid formation. In patients with FAP, albumin was significantly oxidized as the disease progressed. Moreover, loss of functional albumin accelerated TTR deposition in analbuminemic rats possessing a human variant TTR gene. Taken together, these results indicate that albumin may have an inhibitory role in the TTR amyloid-formation process.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Kugimiya
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Shiori
authors.initials: S
authors.lastname: Saito
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kadowaki
authors.forename: Yohei
authors.initials: Y
authors.lastname: Misumi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Hoshii
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tasaki
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Shono
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018384:Oxidative Stress; D011228:Prealbumin / Q000276:immunology / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
chemical_list: D000682:Amyloid; D000975:Antioxidants; D011228:Prealbumin