Aged dysfunctional repair Schwann cells may have a role in transthyretin (TTR) amyloid deposition in the peripheral nervous system of patients with hereditary transthyretin amyloidosis (hATTR), according to a new study published in Neurochemistry International.
The study was conducted by researchers from Japan who developed an immortalized Schwann cell-like phenotype cell line derived from an hATTR mouse model.
“TTR is likely important for axonal regeneration in injured nerves. Secretion of variant TTR by repair Schwann cells might enhance the deposition of TTR aggregates in the peripheral and autonomic nervous systems at the preclinical or early stages of [hATTR],” the researchers said.
They used a small interfering RNA to silence the expression of heat shock transcription factor 1 (HSF1) in the Schwann cell-like cells and found that HSF1 downregulation led to the formation of intracellular TTR aggregates.
Read more about hATTR etiology
Moreover, the researchers found that the Schwann cell-like cells expressed and secreted the TTR protein and that human TTR gene expression was increased by up to 1700-fold when these cells were cultured in nongrowth medium, compared to Schwann cell-like cells cultured in Schwann cell medium.
Schwann cell-like cells cultured in nongrowth medium also showed increased expression of the pan-Schwann cell marker SOX10 and the immature/nonmyelinating Schwann cell marker gene NGFR, as well as decreased expression of the myelin protein gene MPZ, when compared to Schwann cell-like cells cultured in Schwann cell medium. This suggests that the differentiation state of Schwann cell-like cells was altered in nongrowth culture conditions.
Further gene expression analysis identified alterations in several genes associated with the repair program after peripheral nerve injury, indicating that the cellular model used in the study exhibited Schwann cell-like features in nongrowth medium.
Murakami T, Ito Y, Sango K, Watabe K, Sunada Y. Human transthyretin gene expression is markedly increased in repair Schwann cells in an in vitro model of hereditary transthyretin amyloidosis. Neurochem Int. 2023;164:105507. doi:10.1016/j.neuint.2023.105507