Clusterin regulates transthyretin amyloidosis

Ko Woon Lee, Dong Hoon Lee, Hosun Son, Yoon Sook Kim, Jae-Yong Park, Gu Seob Roh, Hyun Joon Kim, Sang Soo Kang, Gyeong Jae Cho, Wan Sung Choi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Transthyretin (TTR) is a human disease-associated amyloidogenic protein that has been implicated in senile systemic amyloidosis (SSA) and familial amyloidotic polyneuropathy (FAP). FAP typically results in severe and early-onset disease, and the only therapy established so far is liver transplantation; thus, developing new strategies for treating FAP is of paramount interest. Clusterin has recently been proposed to play a role as an extracellular molecular chaperone, affecting the fibril formation of amyloidogenic proteins. The ability of clusterin to influence amyloid fibril formation prompted us to investigate whether clusterin is capable of inhibiting TTR amyloidosis. Here, we report that clusterin strongly interacts with wild-type TTR and TTR variants V30M and L55P under acidic conditions, and blocks the amyloid fibril formation of TTR variants. In particular, the amyloid fibril formation of V30M TTR in the presence of clusterin is reduced to level similar to wild-type TTR. We also demonstrated that clusterin is an effective inhibitor of L55P TTR amyloidosis, the most aggressive form of TTR diseases. The mechanism by which clusterin inhibits TTR amyloidosis appears to be through stabilization of TTR tetrameric structure. These findings suggest the possibility of using clusterin as a therapeutic agent for TTR amyloidosis.

Original languageEnglish
Pages (from-to)256-260
Number of pages5
JournalBiochemical and biophysical research communications
Volume388
Issue number2
DOIs
Publication statusPublished - 2009 Oct 16
Externally publishedYes

Fingerprint

Familial Amyloid Neuropathies
Clusterin
Prealbumin
Amyloidosis
Tumor Cell Line
Amyloid
Polyneuropathies
Amyloidogenic Proteins
Molecular Chaperones
Amyloidosis, Hereditary, Transthyretin-Related
Liver Transplantation

Keywords

  • Amyloidosis
  • Clusterin
  • Transthyretin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, K. W., Lee, D. H., Son, H., Kim, Y. S., Park, J-Y., Roh, G. S., ... Choi, W. S. (2009). Clusterin regulates transthyretin amyloidosis. Biochemical and biophysical research communications, 388(2), 256-260. https://doi.org/10.1016/j.bbrc.2009.07.166

Clusterin regulates transthyretin amyloidosis. / Lee, Ko Woon; Lee, Dong Hoon; Son, Hosun; Kim, Yoon Sook; Park, Jae-Yong; Roh, Gu Seob; Kim, Hyun Joon; Kang, Sang Soo; Cho, Gyeong Jae; Choi, Wan Sung.

In: Biochemical and biophysical research communications, Vol. 388, No. 2, 16.10.2009, p. 256-260.

Research output: Contribution to journalArticle

Lee, KW, Lee, DH, Son, H, Kim, YS, Park, J-Y, Roh, GS, Kim, HJ, Kang, SS, Cho, GJ & Choi, WS 2009, 'Clusterin regulates transthyretin amyloidosis', Biochemical and biophysical research communications, vol. 388, no. 2, pp. 256-260. https://doi.org/10.1016/j.bbrc.2009.07.166
Lee, Ko Woon ; Lee, Dong Hoon ; Son, Hosun ; Kim, Yoon Sook ; Park, Jae-Yong ; Roh, Gu Seob ; Kim, Hyun Joon ; Kang, Sang Soo ; Cho, Gyeong Jae ; Choi, Wan Sung. / Clusterin regulates transthyretin amyloidosis. In: Biochemical and biophysical research communications. 2009 ; Vol. 388, No. 2. pp. 256-260.
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