Coordination Funds

轻链或AL淀粉样变性是德国最丰富的系统性淀粉样变性类型之一。严重的肾脏或心脏受累可导致快速透析或死亡。这种疾病是由抗体轻链的错误折叠和聚集引起的，抗体轻链是在单克隆性B细胞疾病过程中产生的。AL淀粉样变性的一个显著特征是其临床表现的多变性。这种异质性可能是由轻链和多态聚集体结构的自然多样性造成的。然而，到目前为止，人们还不清楚确切的关系。这项研究旨在阐明两种特别突出的AL淀粉样变性(主要累及心脏或肾脏)的临床形式，疾病和临床表现是如何由蛋白质的生化特性引起的。我们将特别研究序列和一级结构，蛋白质的降解过程，折叠和多态的聚集体结构。广泛的方法论支持我们的研究战略，该战略主要寻求提高基本理解，但也可能为患者创造直接好处，例如在早期诊断方面。

The light chain or AL amyloidosis is one of the most abundant types of systemic amyloidosis in Germany. Advanced kidney or heart involvement can lead to rapid dialysis or death. The disease is caused by the misfolding and aggregation of antibody light chains, which are produced in the course of a monoclonal B-cell disorder. A particular remarkable feature of AL amyloidosis is the variability of its clinical manifestations. This heterogeneity is probably caused by the natural diversity of light chains and of the polymorphic aggregate structure. However, the exact relationships are not so far understood. This research unit aims to clarify for two specifically prominent clinical forms of AL amyloidosis (dominant heart or kidney involvement) how disease and clinical manifestations arise from protein biochemical properties. We will investigate in particular the sequence and primary structure, the proteolytic processing, the folding and the polymorphic aggregate structure. A broad methodological spectrum supports our research strategy which primarily seeks to improve the basic understanding but which may also create direct benefit for patients, for example in the early diagnosis.