Investigation of the role of innate and acquired immune mechanisms in generation or natural clearance of AA amyloid

Current Research Project

Title / Titel: Investigation of the role of innate and acquired immune mechanisms in generation or natural clearance of AA amyloid

Summary / Zusammenfassung: Amyloid, insoluble protein aggregates with high degree of β -sheet structure that arise after misfolding of normally soluble proteins give rise to lethal diseases. AA amyloidosis is a complication to longstanding inflammatory diseases. Protein amyloid A (AA), an N-terminal fragment of the acute phase protein serum amyloid A (SAA) undergoes conformational changes and is deposited as amyloid in tissue. C-terminal proteolytic cleavage of SAA is considered as critical step in AA-pathogenesis. Amyloid deposition is not an irreversible process. Instead, reduction of amyloid mass is observed when inflammation ceases and SAA levels are normalised. Not much is known about the endogenous factors that contribute to amyloid resolution, however macrophages are found in close proximity with amyloid deposits in several types of amyloidosis. They are implicated to be the key players in both amyloid formation as well as natural clearance. The action of macrophages is tightly regulated by other components of innate and acquired immune defence.

The proposed research aim to use selected immune-compromised mice
(1) to pinpoint the role of macrophages in AA amyloid fibril formation
(2) investigate the role of classical and alternative pathway complement activation
(3) investigate the role of immunoglobulins depletion on clearance of AA amyloid

Keywords / Suchbegriffe: amyloid, macrophages, immune system, clearance, complements system

Project Leadership and Contacts / Projektleitung und Kontakte

Dr. Jana Sponarova (Project Leader)

Funding Source(s) / Unterstützt durch: Others
FEBS Federation of the Societies of Biochemistry and Molecular Biology