XXXX : current views on pathogenesis and impact on diagnosis.

@entity23006 @entity12042 @entity5085 @entity2783
The @entity2783 constitute a group of diseases in which misfolding of extracellular proteins plays a fundamental role. The aggregation of normally soluble proteins into insoluble unbranching fibrils is the basic underlying pathology in @entity2783 . The process of amyloid formation generates toxic insoluble (in saline) protein aggregates that are deposited in tissues in the form of b- pleated sheets of fibrillary material. The @entity2783 are considered to be part of the so-called protein storage diseases (protein thesauroses). In addition, due to the unusual protein folding associated with amyloid, this group of diseases has been referred to as conformational and @entity5085 . For many years @entity2783 was considered an extremely rare, somewhat @entity23006 . However, in recent years its pathogenesis, particularly that of @entity12042 , has been carefully dissected in the research laboratory using in vitro and, to a lesser extent, in vivo models. These have provided a molecular understanding of sequential events that take place in the renal mesangium leading to the formation of amyloid fibrils and eventual extrusion into the mesangial matrix, which itself becomes seriously damaged and, in due time, replaced by the fibrillary material. Amyloid, once considered to be an 'inert' substance, has been proven to be involved in crucial biological processes that result in the destruction and eventual replacement of normal renal constituents. Although there are more than two dozen recognized amyloid precursor proteins (and new ones being added to the list) that can be involved in the genesis of amyloid fibrils, the pathophysiologic mechanisms that occur in the renal mesangium are likely to be very similar, if not the same, regardless of the type of @entity2783 . Likewise, the same is true of amyloid formation in the renal vasculature. Mesangial cells are essentially smooth muscle cells and the events that take place in the mesangium and vasculature (where smooth muscle cells and/or pericytes are present) in the entire body responsible for the formation of amyloid are the same. In the renal interstitium, fibroblasts likely participate in the formation of amyloid, following a similar sequence of events as smooth muscle cells. Although much of the information gathered has been from in vitro systems, an in vivo model of @entity12042 has recently been designed to study renal amyloidogenesis. Crucial steps in the cascade of events that result in the formation of amyloid fibrils have been elucidated in the laboratory. The information that has been gathered regarding the pathogenesis of @entity2783 has been translated to the clinical arena where implementation of new therapeutic approaches is beginning to occur. Additional molecular-based therapies will be implemented in the near future.
