Systemic Amyloidosis: a Contemporary Overview

Abstract

Amyloidosis constitutes a large spectrum of diseases characterized by an extracellular deposition of a fibrillar aggregate, generating insoluble and toxic amasses that may be deposited in tissues in bundles with an abnormal cross-β-sheet conformation, known as amyloid. Amyloid may lead to a cell damage and an impairment of organ function. Several different proteins are recognized as able to produce amyloid fibrils with a different tissue tropism related to the molecular structure. The deposition of amyloid may occur as a consequence of the presence of an abnormal protein, caused by high plasma levels of a normal protein, or as a result of the aging process along with some environmental factors. Although amyloidosis is rare, amyloid deposits play a role in several conditions as degenerative diseases. Thus, the development of antiamyloid curative treatments may be a rational approach to treat neurodegenerative conditions like Alzheimer's disease in the future. Nowadays, novel treatment options are currently refined through controlled trials, as new drug targets and different therapeutic approaches have been identified and validated through modern advances in basic research. Fibril formation stabilizers, proteasome inhibitors, and immunotherapy revealed promising results in improving the outcomes of patients with systemic amyloidosis, and these novel algorithms will be effectively combined with current treatments based on chemotherapeutic regimens. The aim of this review is to provide an update on diagnosis and treatment for systemic amyloidosis.

Keywords: Cardiac amyloidosis; Etanercept; Kinetic stabilization; Proteasome inhibitor; Systemic amyloidosis; Tafamidis.