Skip to main content
SpringerLink
Log in
Book cover

Schwann Cell Development and Pathology pp 103–119Cite as

Expression of the Transthyretin Gene in Schwann Cells and Familial Amyloidotic Polyneuropathy-Mediated Neurodegeneration

  • Chapter
  • First Online:

Abstract

Familial amyloidotic polyneuropathy (FAP) is a hereditary systemic amyloidosis, characterized by peripheral neuropathy. Amyloid derived from most types of FAP consists of transthyretin (TTR) variants with single amino-acid substitutions. Patients with FAP typically show early features of sensory polyneuropathy and autonomic neuropathy. Studies have shown that TTR is mainly produced in the liver and choroid plexus, but not in the peripheral nervous system. However, using laser capture microdissection and reverse transcription-polymerase chain reaction, our group recently discovered the expression of the TTR gene in peripheral glial cells of the dorsal root ganglia. However, the source of TTR amyloid deposits may not be restricted to this cell type, as subsequent studies have revealed that the TTR gene is also expressed in Schwann cells of peripheral nerves. Pathological studies on FAP have shown that the neuropathy is primarily axonopathy, despite numerous studies revealing demyelination and Schwann cell abnormalities. TTR amyloid deposits were observed to have a close association with Schwann cells. TTR synthesis in Schwann cells may therefore explain why TTR variants accumulate in the peripheral nervous system in FAP. In this review, we discuss a relationship between expression of the TTR gene in Schwann cells and the pathogenesis of FAP.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Andersson R (1970) Hereditary amyloidosis with polyneuropathy. Acta Med Scand 188:85–94

    Article  Google Scholar 

  • Andersson K, Olofsson A, Nielsen EH, Svehag SE, Lundgren E (2002) Only amyloidogenic intermediates of transthyretin induce apoptosis. Biochem Biophys Res Commun 294:309–314

    Article  CAS  PubMed  Google Scholar 

  • Andrade C (1952) A peculiar form of peripheral neuropathy; familiar atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain 75:408–427

    Article  CAS  PubMed  Google Scholar 

  • Araki S, Mawatari S, Ohta M, Nakajima A, Kuroiwa Y (1968) Polyneuritic amyloidosis in a Japanese family. Arch Neurol 18:593–602

    Article  CAS  PubMed  Google Scholar 

  • Benson MD (2013) Liver transplantation and transthyretin amyloidosis. Muscle Nerve 47:157–162

    Article  CAS  PubMed  Google Scholar 

  • Blay P, Nilsson C, Owman C, Aldred A, Schreiber G (1993) Transthyretin expression in the rat brain: effect of thyroid functional state and role in thyroxine transport. Brain Res 632:114–120

    Article  CAS  PubMed  Google Scholar 

  • Britsch S, Goerich DE, Riethmacher D, Peirano RI, Rossner M, Nave K-A, Birchmeier C, Wegner M (2001) The transcription factor Sox10 is a key regulator of peripheral glial development. Genes Dev 15:66–78

    Google Scholar 

  • Carvalho J, Coimbra A, Andrade C (1976) Peripheral nerve fibre changes in asymptomatic children of patients with familial amyloid polyneuropathy. Brain 99:1–10

    Article  CAS  PubMed  Google Scholar 

  • Coimbra A, Andrade C (1971a) Familial amyloid polyneuropathy: an electron microscope study of the peripheral nerve in five cases. I. Interstitial changes. Brain 94:199–206

    Article  CAS  PubMed  Google Scholar 

  • Coimbra A, Andrade C (1971b) Familial amyloid polyneuropathy: an electron microscope study of the peripheral nerve in five cases. II. Nerve fibre changes. Brain 94:207–212

    Article  CAS  PubMed  Google Scholar 

  • Connors LH, Lim A, Prokaeva T, Roskens VA, Costello CE (2003) Tabulation of human transthyretin (TTR) variants, 2003. Amyloid 10:160–184

    Article  CAS  PubMed  Google Scholar 

  • Costa PP, Figueira AS, Bravo FR (1978) Amyloid fibril protein related to prealbumin in familial amyloidotic polyneuropathy. Proc Natl Acad Sci USA 75:4499–4503

    Article  CAS  PubMed  Google Scholar 

  • Dyck PJ, Lambert EH (1969) Dissociated sensation in amylidosis. Compound action potential, quantitative histologic and teased-fiber, and electron microscopic studies of sural nerve biopsies. Arch Neurol 20:490–507

    Article  CAS  PubMed  Google Scholar 

  • Dyck PJ, Dyck PJB, Engelstad J (2005) Pathologic alterations of nerves. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier, Philadelphia, pp 733–829

    Chapter  Google Scholar 

  • Episkopou V, Maeda S, Nishiguchi S, Shimada K, Gaitanaris GA, Gottesman ME, Robertson EJ (1993) Disruption of the transthyretin gene results in mice with depressed levels of plasma retinol and thyroid hormone. Proc Natl Acad Sci USA 90:2375–2379

    Article  CAS  PubMed  Google Scholar 

  • Fleming CE, Saraiva MJ, Sousa MM (2007) Transthyretin enhances nerve regeneration. J Neurochem 103:831–839

    Article  CAS  PubMed  Google Scholar 

  • Fleming CE, Mar FM, Franquinho F, Saraiva MJ, Sousa MM (2009) Transthyretin internalization by sensory neurons is megalin mediated and necessary for its neuritogenic activity. J Neurosci 29:3220–3232

    Article  CAS  PubMed  Google Scholar 

  • Freeman MR, Sueoka N (1987) Induction and segregation of glial intermediate filament expression in the RT4 family of peripheral nervous system cell lines. Proc Natl Acad Sci USA 84:5808–5812

    Article  CAS  PubMed  Google Scholar 

  • Fung WP, Thomas T, Dickson PW, Aldred AR, Milland J, Dziadek M, Power B, Hudson P, Schreiber G (1988) Structure and expression of the rat transthyretin (prealbumin) gene. J Biol Chem 263:480–488

    CAS  PubMed  Google Scholar 

  • Gasperini RJ, Hou X, Parkington H, Coleman H, Klaver DW, Vincent AJ, Foa LC, Small DH (2011) TRPM8 and Nav1.8 sodium channels are required for transthyretin-induced calcium influx in growth cones of small-diameter TrkA-positive sensory neurons. Mol Neurodegener 6:19

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Guimarães A, Viana Pinheiro A, Leite I (1990) Sural nerve biopsy in familial amyloidotic polyneuropathy: a morphological and morphometric polyneuropathy. In: Natvig JB, Forre O, Hasuby G et al (eds) Amyloid and amyloidosis. Kluwer, London, pp 493–498

    Google Scholar 

  • Hanani M (2005) Satellite glial cells in sensory ganglia: from form to function. Brain Res Rev 48:457–476

    Article  CAS  PubMed  Google Scholar 

  • Hanyu N, Ikeda S, Nakadai A, Yanagisawa N, Powell HC (1989) Peripheral nerve pathological findings in familial amyloid polyneuropathy: a correlative study of proximal sciatic nerve and sural nerve lesions. Ann Neurol 25:340–350

    Article  CAS  PubMed  Google Scholar 

  • Hofer PA, Anderson R (1975) Postmortem findings in primary familial amyloidosis with polyneuropathy. Acta Pathol Microbiol Scand A 83:309–322

    CAS  PubMed  Google Scholar 

  • Ikeda S, Hanyu N, Hongo M, Yoshioka J, Oguchi H, Yanagisawa N, Kobayashi T, Tsukagoshi H, Ito N, Yokota T (1987) Hereditary generalized amyloidosis with polyneuropathy. Clinicopathological study of 65 Japanese patients. Brain 110:315–337

    Article  PubMed  Google Scholar 

  • Inoue S, Kuroiwa M, Saraiva MJ, Guimarães A, Kisilevsky R (1998) Ultrastructure of familial amyloid polyneuropathy amyloid fibrils: examination with high-resolution electron microscopy. J Struct Biol 124:1–12

    Article  CAS  PubMed  Google Scholar 

  • Jacobsson B (1989) In situ localization of transthyretin-mRNA in the adult human liver, choroid plexus and pancreatic islets and in endocrine tumours of the pancreas and gut. Histochemistry 91:299–304

    Article  CAS  PubMed  Google Scholar 

  • Jedrzejowska H (1977) Some histological aspects of amyloid polyneuropathy. Acta Neuropathol 37:119–125

    Article  CAS  PubMed  Google Scholar 

  • Jessen KR, Mirsky R (2005) The origin and development of glial cells in peripheral nerves. Nat Rev 6:671–682

    Article  CAS  Google Scholar 

  • Kohno K, Palha JA, Miyakawa K, Saraiva MJ, Ito S, Mabuchi T, Blaner WS, Iijima H, Tsukahara S, Episkopou V, Gottesman ME, Shimada K, Takahashi K, Yamamura K, Maeda S (1997) Analysis of amyloid deposition in a transgenic mouse model of homozygous familial amyloidotic polyneuropathy. Am J Pathol 150:1497–1508

    CAS  PubMed  Google Scholar 

  • Koike H, Misu K, Sugiura M, Iijima M, Mori K, Yamamoto M, Hattori N, Mukai E, Ando Y, Ikeda S, Sobue G (2004) Pathology of early- vs. late-onset TTR Met30 familial amyloid polyneuropathy. Neurology 63:129–138

    Article  CAS  PubMed  Google Scholar 

  • Koike H, Hashimoto R, Tomita M, Kawagashira Y, Iijima M, Nakamura T, Watanabe H, Kamei H, Kiuchi T, Sobue G (2012) Impact of aging on the progression of neuropathy after liver transplantation in transthyretin Val30Met amyloidosis. Muscle Nerve 46:964–970

    Article  CAS  PubMed  Google Scholar 

  • Luis ML (1978) Electroneurophysiological studies in familial amyloid polyneuropathy–Portuguese type. J Neurol Neurosurg Psychiatry 41:847–850

    Article  CAS  PubMed  Google Scholar 

  • Martone RL, Herbert J, Dwork A, Schon EA (1988) Transthyretin is synthesized in the mammalian eye. Biochem Biophys Res Commun 151:905–912

    Article  CAS  PubMed  Google Scholar 

  • Matsumura K, Chiba A, Yamada H, Fukuta-Ohi H, Fujita S, Endo T, Kobata A, Anderson LV, Kanazawa I, Campbell KP, Shimizu T (1997) A role of dystroglycan in schwannoma cell adhesion to laminin. J Biol Chem 272:13904–13910

    Article  CAS  PubMed  Google Scholar 

  • Mita S, Maeda S, Shimada K, Araki S (1984) Cloning and sequence analysis of cDNA for human prealbumin. Biochem Biophys Res Commun 124:558–564

    Article  CAS  PubMed  Google Scholar 

  • Mita S, Maeda S, Shimada K, Araki S (1986) Analyses of prealbumin mRNAs in individuals with familial amyloidotic polyneuropathy. J Biochem 100:1215–1222

    CAS  PubMed  Google Scholar 

  • Murakami T, Yasuda Y, Mita S, Maeda S, Shimada K, Fujimoto T, Araki S (1987) Prealbumin gene expression during mouse development studied by in situ hybridization. Cell Differ 22:1–9

    Article  CAS  PubMed  Google Scholar 

  • Murakami T, Uchino M, Ando M (1995) Genetic abnormalities and pathogenesis of familial amyloidotic polyneuropathy. Pathol Int 45:1–9

    Article  CAS  PubMed  Google Scholar 

  • Murakami T, Ohsawa Y, Sunada Y (2008) The transthyretin gene is expressed in human and rodent dorsal root ganglia. Neurosci Lett 436:335–339

    Article  CAS  PubMed  Google Scholar 

  • Murakami T, Ohsawa Y, Sunada Y (2009) Reevaluation of transthrein gene expression in the nervous system: the expression in dorsal root ganglia. Peripher Nerv 20:30–35

    Google Scholar 

  • Murakami T, Ohsawa Y, Zhenghua L, Yamamura K, Sunada Y (2010) The transthyretin gene is expressed in Schwann cells of peripheral nerves. Brain Res 1348:222–225

    Article  CAS  PubMed  Google Scholar 

  • Nagasaka T, Togashi S, Watanabe H, Iida H, Nagasaka K, Nakamura Y, Miwa M, Kobayashi F, Shindo K, Shiozawa Z (2009) Clinical and histopathological features of progressive-type familial amyloidotic polyneuropathy with TTR Lys54. J Neurol Sci 276:88–94

    Article  CAS  PubMed  Google Scholar 

  • Planté-Bordeneuve V, Said G (2011) Familial amyloid polyneuropathy. Lancet Neurol 10:1086–1097

    Article  PubMed  Google Scholar 

  • Pokrzywa M, Dacklin I, Vestling M, Hultmark D, Lundgren E, Cantera R (2010) Uptake of aggregating transthyretin by fat body in a Drosophila model for TTR-associated amyloidosis. PLoS One 5:e14343

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Prokunina L, Gaspari M, Thyén C (2002) Of mice and men: the case of differential regulation of the TTR gene. In: Abstracts of the 5th international symposium on familial amyloidotic polyneuropathy and other transthyretin related disorders, Matsumoto, 24–27 Sept 2002

    Google Scholar 

  • Reixach N, Deechongkit S, Jiang X, Kelly JW, Buxbaum JN (2004) Tissue damage in the amyloidoses: transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proc Natl Acad Sci USA 101:2817–2822

    Article  CAS  PubMed  Google Scholar 

  • Said G (2003) Familial amyloid polyneuropathy: mechanisms leading to nerve degeneration. Amyloid 10(suppl 1):7–12

    PubMed  Google Scholar 

  • Said G, Planté-Bordeneuve V (2009) Familial amyloid polyneuropathy: a clinico-pathologic study. J Neurol Sci 284:149–154

    Article  CAS  PubMed  Google Scholar 

  • Said G, Ropert A, Faux N (1984) Length-dependent degeneration of fibers in Portuguese amyloid polyneuropathy: a clinicopathologic study. Neurology 34:1025–1032

    Article  CAS  PubMed  Google Scholar 

  • Santos SD, Fernandes R, Saraiva MJ (2010) The heat shock response modulates transthyretin deposition in the peripheral and autonomic nervous systems. Neurobiol Aging 31:280–289

    Article  CAS  PubMed  Google Scholar 

  • Sobue G, Shuman S, Pleasure D (1986) Schwann cell responses to cyclic AMP: proliferation, change in shape, and appearance of surface galactocerebroside. Brain Res 362:23–32

    Article  CAS  PubMed  Google Scholar 

  • Sobue G, Nakao N, Murakami K, Yasuda T, Sahashi K, Mitsuma T, Sasaki H, Sakaki Y, Takahashi A (1990) Type I familial amyloid polyneuropathy. A pathological study of the peripheral nervous system. Brain 113:903–919

    Article  PubMed  Google Scholar 

  • Soprano DR, Herbert J, Soprano KJ, Schon EA, Goodman DS (1985) Demonstration of transthyretin mRNA in the brain and other extrahepatic tissues in the rat. J Biol Chem 260:11793–11798

    CAS  PubMed  Google Scholar 

  • Sousa MM, Saraiva MJ (2003) Neurodegeneration in familial amyloid polyneuropathy: from pathology to molecular signaling. Prog Neurobiol 71:385–400

    Article  CAS  PubMed  Google Scholar 

  • Sousa MM, Saraiva MJ (2008) Transthyretin is not expressed by dorsal root ganglia cells. Exp Neurol 214:362–365

    Article  CAS  PubMed  Google Scholar 

  • Sousa MM, Cardoso I, Fernandes R, Guimarães A, Saraiva MJ (2001a) Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy: evidence for toxicity of nonfibrillar aggregates. Am J Pathol 159:1993–2000

    Article  CAS  PubMed  Google Scholar 

  • Sousa MM, Du Yan S, Fernandes R, Guimarães A, Stern D, Saraiva MJ (2001b) Familial amyloid polyneuropathy: receptor for advanced glycation end products-dependent triggering of neuronal inflammatory and apoptotic pathways. J Neurosci 21:7576–7586

    CAS  PubMed  Google Scholar 

  • Sousa MM, Fernandes R, Palha JA, Taboada A, Vieira P, Saraiva MJ (2002) Evidence for early cytotoxic aggregates in transgenic mice for human transthyretin Leu55Pro. Am J Pathol 161:1935–1948

    Article  CAS  PubMed  Google Scholar 

  • Sousa JC, Cardoso I, Marques F, Saraiva MJ, Palha JA (2007) Transthyretin and Alzheimer’s disease: where in the brain? Neurobiol Aging 28:713–718

    Article  CAS  PubMed  Google Scholar 

  • Suhr OB (2003) Impact of liver transplantation on familial amyloidotic polyneuropathy (FAP) patients’ symptoms and complications. Amyloid 10(suppl 1):77–83

    PubMed  Google Scholar 

  • Takahashi K, Nakamura H, Ishitobi K, Harada Y (1974) Ultrastrurcture of sural nerves of amyloid neuropathy with special reference to an asymptomatic sibling. Clin Neurol 14:266–274

    CAS  Google Scholar 

  • Takahashi K, Yi S, Kimura Y, Araki S (1991) Familial amyloidotic polyneuropathy type 1 in Kumamoto, Japan: a clinicopathologic, histochemical, immunohistochemical, and ultrastructural study. Hum Pathol 22:519–527

    Article  CAS  PubMed  Google Scholar 

  • Tawara S, Nakazato M, Kangawa K, Matsuo H, Araki S (1983) Identification of amyloid prealbumin variant in familial amyloidotic polyneuropathy (Japanese type). Biochem Biophys Res Commun 116:880–888

    Article  CAS  PubMed  Google Scholar 

  • Teixeira PF, Cerca F, Santos SD, Saraiva MJ (2006) Endoplasmic reticulum stress associated with extracellular aggregates. Evidence from transthyretin deposition in familial amyloid polyneuropathy. J Biol Chem 281:21998–22003

    Article  CAS  PubMed  Google Scholar 

  • Thomas PK, King RH (1974) Peripheral nerve changes in amyloid neuropathy. Brain 97:395–406

    Article  CAS  PubMed  Google Scholar 

  • Toyooka K, Fujimura H, Ueno S, Yoshikawa H, Kaido M, Nishimura T, Yorifuji S, Yanagihara T (1995) Familial amyloid polyneuropathy associated with transthyretin Gly42 mutation: a quantitative light and electron microscopic study of the peripheral nervous system. Acta Neuropathol 90:516–525

    Article  CAS  PubMed  Google Scholar 

  • Wakasugi S, Maeda S, Shimada K, Nakashima H, Migita S (1985) Structural comparisons between mouse and human prealbumin. J Biochem 98:1707–1714

    CAS  PubMed  Google Scholar 

  • Watabe K, Fukuda T, Tanaka J, Honda H, Toyohara K, Sakai O (1995) Spontaneously immortalized adult mouse Schwann cells secrete autocrine and paracrine growth-promoting activities. J Neurosci Res 41:279–290

    Article  CAS  PubMed  Google Scholar 

  • Yamada M, Hatakeyama S, Tsukagoshi H (1984) Peripheral and autonomic nerve lesions in systemic amyloidosis. Three pathological types of amyloid polyneuropathy. Acta Pathol Jpn 34:1251–1266

    CAS  PubMed  Google Scholar 

  • Yamamoto S, Wilczek HE, Nowak G, Larsson M, Oksanen A, Iwata T, Gjertsen H, Söderdahl G, Wikström L, Ando Y, Suhr OB, Ericzon BG (2007) Liver transplantation for familial amyloidotic polyneuropathy (FAP): a single-center experience over 16 years. Am J Transplant 7:2597–2604

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan

    Tatsufumi Murakami & Yoshihide Sunada

Authors
  1. Tatsufumi Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshihide Sunada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tatsufumi Murakami .

Editor information

Editors and Affiliations

  1. Department of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Kazunori Sango

  2. Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo, Japan

    Junji Yamauchi

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Japan

About this chapter

Cite this chapter

Murakami, T., Sunada, Y. (2014). Expression of the Transthyretin Gene in Schwann Cells and Familial Amyloidotic Polyneuropathy-Mediated Neurodegeneration. In: Sango, K., Yamauchi, J. (eds) Schwann Cell Development and Pathology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54764-8_7

Download citation

Publish with us

Policies and ethics

Search

Navigation