Abstract
Transthyretin (TTR)-familial amyloid polyneuropathy (FAP) is a systemic amyloidosis caused by mutations in the TTR gene. Typically, patients initially present with sensory and autonomic symptoms, which can lead to sensory dominant polyneuropathy and autonomic neuropathy. Mutations in TTR cause the tetrameric protein to dissociate and form amyloid deposits in the peripheral nervous system, most prominently in dorsal root ganglia (DRG), autonomic ganglia, and nerve trunks. Teased fiber studies have shown that segmental demyelination and axonal degeneration preferentially occur in the proximal and distal regions of the peripheral nerves, respectively. Nevertheless, it remains unknown why genetic variants of TTR lead to neurodegeneration in the peripheral nervous system. Recent studies in our laboratory have uncovered an important role for Schwann cells in the disease progression of FAP. In this review, we summarize findings implicating Schwann cells in FAP, and provide evidence that DRG may serve as the initial site of lesion formation in the disease.
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Acknowledgments
This work is supported by Research Project Grants from Kawasaki Medical School [29-046]; and KAKENHI [16 K09686]. We thank Travis J. Bernardo, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
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Murakami, T., Sunada, Y. (2019). Transthyretin Amyloid Neuropathy: The Schwann Cell Hypothesis. In: Sango, K., Yamauchi, J., Ogata, T., Susuki, K. (eds) Myelin. Advances in Experimental Medicine and Biology, vol 1190. Springer, Singapore. https://doi.org/10.1007/978-981-32-9636-7_24
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