EGCG AL Amyloidosis

Inhibition of amyloid fibril formation could benefit patients with systemic amyloidosis. In this group of diseases, deposition of amyloid fibrils derived from normally soluble proteins leads to progressive tissue damage and organ failure. Amyloid formation is a complex process, where several individual steps could be targeted. Several small molecules have been proposed as inhibitors of amyloid formation. However, the exact mechanism of action for a molecule is often not known, which impedes medicinal chemistry efforts to develop more potent molecules...

INTRODUCTION: Deciphering the intricacies of the interactions of glomerulopathic Ig light chains with mesangial cells is key to delineate signaling events responsible for the mesangial pathologic alterations that ensue. METHODS: Human mesangial cells, caveolin 1 (CAV1), wild type (WT) ,and knockout (KO), were incubated with glomerulopathic light chains purified from the urine of patients with light chain-associated (AL) amyloidosis or light chain deposition disease...

BACKGROUND: Light chains are abnormally overexpressed from disordered monoclonal B-cells and form amyloid fibrils, which are then deposited on the affected organ, leading to a form of systemic amyloidosis known as AL (Amyloid Light chain) amyloidosis. A green tea catechin, epigallocatechin-3-O-gallate (EGCG), which is thought to inhibit various amyloidoses, is a potent inhibitor of amyloid fibril formation in AL amyloidosis. METHODS: An amyloidogenic variable domain in λ6 light chain mutant, Wil was incubated in the presence of EGCG...

Intervention into amyloid deposition with anti-amyloid agents like the polyphenol epigallocatechin-3-gallate (EGCG) is emerging as an experimental secondary treatment strategy in systemic light chain amyloidosis (AL). In both AL and multiple myeloma (MM), soluble immunoglobulin light chains (LC) are produced by clonal plasma cells, but only in AL do they form amyloid deposits in vivo We investigated the amyloid formation of patient-derived LC and their susceptibility to EGCG in vitro to probe commonalities and systematic differences in their assembly mechanisms...

Previous studies have suggested that an increase in mitochondrial reactive oxygen species may cause organ damage in patients with light-chain (AL) amyloidosis; however, this damage can be decreased by antioxidant-agent treatment. Epigallocatechin gallate (EGCG), the major natural catechin in green tea, has potent antioxidant activity. Because EGCG has recently been reported to have a favorable toxicity profile for treating amyloidosis, we sought to examine the clinical efficacy and toxicity of EGCG in patients with AL amyloidosis...

Light chain amyloidosis (AL) is a deadly disease characterized by the deposition of monoclonal immunoglobulin light chains as insoluble amyloid fibrils in different organs and tissues. Germ line λ VI has been closely related to this condition; moreover, the R24G mutation is present in 25% of the proteins of this germ line in AL patients. In this work, five small molecules were tested as inhibitors of the formation of amyloid fibrils from the 6aJL2-R24G protein. We have found by thioflavin T fluorescence and transmission electron microscopy that EGCG inhibits 6aJL2-R24G fibrillogenesis...

BACKGROUND: Amyloid light chain (AL) amyloidosis is a rare disease with poor prognosis and limited therapeutic alternatives. Recently, one clinical case with cardiac involvement, as well as a compelling evidence of green tea polyphenol, epigallocatechin-3-gallate (EGCG), inducing the formation of benign aggregation products that do not polymerize into fibrils were published. This is a report of the cardiac effects of green tea consumption in these patients. METHODS: Patients with known cardiac involvement in AL amyloidosis were examined by routine cardiovascular examinations that took place every 3-6 months...