INFORMAZIONI SU
PINZON RAMIREZ Juan Sebastian
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Supervisore:Prf.ssa Corazza Immunoglobulin Light Chain Characterization through NMR Techniques and Evaluation of Associated Molecular Mechanisms |
| Light chain (AL) amyloidosis is a systemic disease caused by the accumulation of homodimers of immunoglobulin G (IgG) light chains synthesized by malignant plasma cells. Studies have reported amyloid formation associated with mutations in the variable domains of IgG light chains compared to germline genes. Additionally, truncated forms of pathological dimers have been identified in fibrils extracted from patients, suggesting the involvement of proteases capable of cleaving near the constant domain of the light chains. The first objective of my work is to characterize the structure of the entire light chain, comprising both variable and constant domains, using NMR techniques. The focus then shifts to examining the interaction between the light chain and other partners that might be relevant in the fibril formation of the full length light chain. Finally, the study aims to elucidate the molecular mechanisms underlying fibril formation and the possible role of proteases in this process, assessing whether proteolytic activity is a prerequisite for fibrillogenesis or a downstream effect associated with the immune recognition of amyloids as non-self structures. |
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