From the Light Chain Sequence to the Tissue Microenvironment: Contribution of the Mesangial Cells to Glomerular Amyloidosis

Hemato

Elba A. Turbat-Herrera¹  Luis Del Pozo-Yauner¹  Guillermo A. Herrera¹  Julio I. Pérez-Carreón² 

[1] Department of Pathology, College of Medicine, University of South Alabama, Mobile, AL 36617, USA;Laboratory of Liver Diseases, National Institute of Genomic Medicine, Tlalpan, Ciudad de Mexico 14610, Mexico;

关键词: light chain;    amyloidosis;    AL fibril;    mesangial cell;    protein aggregation;    protein misfolding;   

DOI  :  10.3390/hemato3010019

来源: DOAJ

【 摘 要 】

Studies carried out in the last three decades have significantly advanced our knowledge about the structural factors that drive the amyloid aggregation of the immunoglobulin light chains. Solid-state nuclear magnetic resonance and cryo-electron microscopy studies have resulted in huge progress in our knowledge about the AL fibril structure. Now, it is known that the assembly of the light chain into AL fibrils implies an extensive conformational rearrangement that converts the beta-sandwich fold of the protein into a near flat structure. On the other hand, there has also been significant progress made in understanding the role that some cell types play as facilitators of AL formation. Such a role has been studied in glomerular amyloidosis, where mesangial cells play an important role in the mechanism of AL deposition, as well as for the pathogenic mechanisms that result in glomerular/renal damage. This review addresses what we currently know about why and how certain light chains are prone to forming amyloid. It also summarizes the most recent publications on the structure of AL fibrils and analyzes the structural bases of this type of aggregate, including the origin of its structural diversity. Finally, the most relevant findings on the role of mesangial cells in the amyloid deposition of light chains in the glomerular space are summarized.

【 授权许可】

Unknown