Exploring critical determinants of protein amyloidogenesis: a review

Abstract

The transformation of polypeptide chains from their globular native structure to fibrillar aggregates has been a matter of great concern because of the involvement of these aggregates in the onset of several degenerative diseases. These aggregates exhibit highly ordered cross β sheet structures and are known as 'amyloids'. Formation of amyloids in the body is associated with cytotoxicity due to direct interaction of the aggregated species with the cell membrane leading to cellular permeability or due to loss of functionality of the proteins involved in the amyloid formation. The preference of polypeptide chains to remain in their native conformation or to aggregate into amyloids is guided by several factors such as its conformation at specific condition, concentration, physicochemical properties of the amino acid sequence and so on. In the current review, we have reviewed the different factors that guide the transition of proteins from their natively folded state to the amyloidogenic state. Understanding the critical determinants of amyloidogenesis is vital towards deciphering the molecular mechanism of amyloidogenesis and for the development of effective therapeutics against amyloidosis.

Amyloid associated with neoplasia in two captive tricolour sharkminnows Balantiocheilus melanopterus Bleeker

“…In that fish, amyloid was present in several tissues including the liver, spleen, heart, kidney and vasculature, and the protein deposits were believed to have impaired cardiac and renal function. Clinical manifestations of disease occur through the accumulation of fibrils and misfolded amyloidogenic proteins that disrupt organ structure and function rather than through direct cytotoxic effects (Sakar & Dubey 2013). Conversely, amyloid deposits composed of various proteins that occur within neoplastic lesions, and arterial walls can be incidental and not necessarily pathogenic (Pepys 2006).…”

Amyloid-based nanosensors and nanodevices

“…[85][86][87][88] It is less known that amyloids are also involved in non-pathological events. These amyloids, also named ''functional amyloids'', seem to exert regular biological functions.…”

Minimally Invasive Minor Salivary Gland Biopsy for the Diagnosis of Amyloidosis in a Rheumatology Clinic

“…A substantial number of our patients had FMF as underlying disorder which is somewhat different from other geographic regions [10, 16]. However, we do not think that it is a major concern since the mechanism leading to amyloidosis is persistent inflammation as observed in other rheumatic diseases [17]. Tissue biopsies other than MSGB were not routinely performed in all patients; therefore, we could not compare sensitivity and specificity of MSGB with other biopsy sites.…”