Pharmacologic targeting of plasma cell endoplasmic reticulum proteostasis to reduce amyloidogenic light chain secretion.

ABSTRACT: Light chain (LC) amyloidosis (AL) involves the toxic aggregation of amyloidogenic immunoglobulin LCs secreted from a clonal expansion of diseased plasma cells. Current AL treatments use chemotherapeutics to ablate the AL plasma cell population. However, no treatments are available that directly reduce the toxic LC aggregation involved in AL pathogenesis. An attractive strategy to reduce toxic LC aggregation in AL involves enhancing endoplasmic reticulum (ER) proteostasis in plasma cells to reduce the secretion and subsequent aggregation of amyloidogenic LCs. Here, we show that the ER proteostasis regulator compound 147 reduces secretion of an amyloidogenic LC as aggregation-prone monomers and dimers in AL patient-derived plasma cells. Compound 147 was established to promote ER proteostasis

SUBMITTER: Rius B 

PROVIDER: S-EPMC7903236 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature