Dendrimers antiamyloidogenic potential in neurodegenerative diseases

Abstract

Dendrimers have been shown to be capable of interfering in vitro with the formation of the amyloid fibrillar structures typically related to the onset and development of the so-called conformational diseases, such as Alzheimer's disease and prion diseases. This makes dendrimers potentially useful as compounds that could prevent or inhibit the action of the cytotoxic amyloid species. In the present paper we summarise the works on the interaction of dendrimers with amyloid peptides related to Alzheimer and prion diseases and take it as the basis from which to focus on some developments that will contribute to enhance the potential of dendrimers as antiamyloidogenic agents. An important first set of works was dedicated to the characterization of the effects of positively charged PAMAM and phosphorous dendrimers on the polymerization processes of different amyloid peptides. However, due to the inherent toxicity of positively charged dendrimers, the research has moved towards the design of more biocompatible dendrimers such as glycodendrimers. This sugar-decorated dendrimers have shown as well their capacity to interact with amyloids, a low level of cell toxicity has been measured for different cell lines and they have shown interesting properties as antiamyloidogenic agents. Other surface-decorated dendrimeric structures are finally also taken into account.