Biomedical Engineering Reference
In-Depth Information
Chapter 2
Protein Aggregation Diseases: Toxicity of Soluble
Prefibrillar Aggregates and Their Clinical Significance
Massimo Stefani
Abstract
Amyloid diseases, the most clinically relevant protein misfolding pathologies due to the high prevalence
of some of them in the population, are characterized by the presence, in specific tissues and organs, of
fibrillar deposits of specific peptides or proteins. Increasing efforts are presently dedicated at investigating
the structural features and the structure-toxicity relation of the soluble oligomeric precursors arising in
the path of fibril formation. In fact, it is increasingly recognised that these unstable, dynamic assemblies
are remarkably toxic to cells thus featuring these as the main factor responsible for cell impairment in
amyloid diseases. This chapter will review shortly the data presently available on the structural and bio-
chemical features of these assemblies, as well as on their biological and clinical significance.
Key words
: Amyloid, Amyloid oligomers, Amyloid fibrils, Amyloid cytotoxicity
1. Introduction
Amyloid diseases are, by far, the most clinically relevant protein
misfolding pathologies due to the high prevalence of some of
them in the population, including type II diabetes mellitus,
Alzheimer's, and Parkinson's diseases. They are characterized by
the presence, either localized or spread in specific tissues and
organs, of fibrillar deposits of specific peptides or proteins
(reviewed in (
1
)). Amyloid fibrils are polymeric assemblies of 1
out of around 20 peptides or proteins, each characteristic of a
specific disease or of a group of strictly similar pathological condi-
tions associated with peculiar clinical signs (reviewed in (
2
)). The
presently described amyloid diseases include over 20 familial,
sporadic, or transmissible conditions, although other degenera-
tive pathologies with amyloid deposition are increasingly being
Search WWH ::
Custom Search