Schwann cells contribute to neurodegeneration in transthyretin amyloidosis. (2nd March 2015)

• Record Type: Journal Article
• Authors: Murakami, Tatsufumi; Sango, Kazunori; Watabe, Kazuhiko; Niimi, Naoko; Takaku, Shizuka; Li, Zhenghua; Yamamura, Ken‐ichi; Sunada, Yoshihide
• Is Part Of: Journal of neurochemistry. Volume 134:Number 1(2015:Jul.)
• Page Start: 66
• Page End: 74
• Publication Date: 2015-03-02
• Subjects: Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.13068
• Languages: English
• ISSNs: 0022-3042

Abstract

<abstract abstract-type="main" id="jnc13068-abs-0001"> <title>Abstract</title> <p>Familial amyloidotic polyneuropathy (FAP) is one of the transthyretin (TTR) amyloidoses characterized by extracellular amyloid deposits and peripheral nerve involvement. Recently, we found significant expression of the <italic>TTR</italic> gene in Schwann cells of the peripheral nervous system. We hypothesized that local expression of variant <italic>TTR</italic> in Schwann cells may contribute to neurodegeneration in FAP. Schwann cells derived from the dorsal root ganglia (DRG) of transgenic mice expressing variant human <italic>TTR</italic> in a mouse null background were cultured long term to obtain spontaneously immortalized cell lines. We established an immortalized Schwann cell line, TgS1, derived from the transgenic mice. TgS1 cells synthesized variant TTR and secreted it into the medium. As sensory neuropathy usually arises early in FAP, we examined the effect of the conditioned medium derived from TgS1 cells on neurite outgrowth from DRG sensory neurons. Conditioned medium derived from TgS1 cells inhibited neurite outgrowth from the sensory neurons. TTR deposition in the DRG of aged transgenic mice was investigated by immunohistochemistry. TTR aggregates were observed in the cytoplasm of Schwann cells and satellite cells. Proteasome inhibition induced TTR aggregates as aggresomes in TgS1 cells. In conclusion, local variant <italic>TTR</italic> gene expression in Schwann cells might trigger neurodegeneration in FAP. <graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgj10cncm16" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></p> <p>We established a spontaneously immortalized Schwann cell line derived from familial amyloidotic polyneuropathy transgenic mice. Conditioned medium from the cells contained variant transthyretin (TTR), and inhibited neurite outgrowth of neurons. TTR aggregates were observed in the Schwann cells and satellite cells of aged mice. Proteasome inhibition induced TTR aggregates as aggresomes in the cultured cells. These results support the hypothesis that Schwann cells contribute to neurodegeneration in familial amyloidotic polyneuropathy (FAP).</p> </abstract>