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Current Drug Targets


ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Towards Understanding the Structure-Function Relationship of Human Amyloid Disease

Author(s): Chris Dealwis and Jonathan Wall

Volume 5, Issue 2, 2004

Page: [159 - 171] Pages: 13

DOI: 10.2174/1389450043490550

Price: $65


Immunoglobulin light chain (LC) proteins exhibit the greatest sequence variability of all proteins associated with amyloid disease. The hallmark event in amyloidogenesis is a change in the secondary and / /or tertiary structure of a normal, soluble protein, that fosters selfaggregation and fibril formation. The structural heterogeneity of light chain proteins has hampered understanding of the precise mechanisms involved in fibril formation. The development of effective therapeutics will be benefited by a fundamental understanding of mechanisms and structural prerequisites which govern amyloidogenesis. This review focuses on light chain (AL) amyloidosis resulting from the aggregation of κ and λ LCs. Specifically the thermodynamic and structural data of several WT and mutant amyloidogenic LCs have been carefully examined. Moreover, we discuss the importance of hydrophobic and ionic interactions on amyloidosis by comparing several available three-dimensional structures of amyloidogenic and highly homologous non-amyloidogenic proteins that can be destabilized to become amyloidogenic by site specific mutations.

Keywords: Human Amyloid Disease, non-amyloidogenic proteins, thermodynamic, amyloidogenesis

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