{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:12:56Z","timestamp":1791252776781,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL57566"],"award-info":[{"award-number":["HL57566"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK46335"],"award-info":[{"award-number":["DK46335"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hemato"],"abstract":"<jats:p>Non-native immunoglobulin light chain conformations, including aggregates, appear to cause light chain amyloidosis pathology. Despite significant progress in pharmacological eradication of the neoplastic plasma cells that secrete these light chains, in many patients impaired organ function remains. The impairment is apparently due to a subset of resistant plasma cells that continue to secrete misfolding-prone light chains. These light chains are susceptible to the proteolytic cleavage that may enable light chain aggregation. We propose that small molecules that preferentially bind to the natively folded state of full-length light chains could act as pharmacological kinetic stabilizers, protecting light chains against unfolding, proteolysis and aggregation. Although the sequence of the pathological light chain is unique to each patient, fortunately light chains have highly conserved residues that form binding sites for small molecule kinetic stabilizers. We envision that such stabilizers could complement existing and emerging therapies to benefit light chain amyloidosis patients.<\/jats:p>","DOI":"10.3390\/hemato2040042","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T21:47:34Z","timestamp":1633988854000},"page":"645-659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Light Chain Stabilization: A Therapeutic Approach to Ameliorate AL Amyloidosis"],"prefix":"10.3390","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1275-2010","authenticated-orcid":false,"given":"Gareth J.","family":"Morgan","sequence":"first","affiliation":[{"name":"Section of Hematology and Medical Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA"},{"name":"The Amyloidosis Center, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel N.","family":"Buxbaum","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery W.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA"},{"name":"The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Systemic Immunoglobulin Light Chain Amyloidosis","volume":"4","author":"Merlini","year":"2018","journal-title":"Nat. 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