Amyloids: Friend or Foe?

Abstract

Amyloidogenesis is the aggregation of soluble proteins into structurally conserved fibers. Amyloid fibers are distinguished by their resistance to proteinase K, tinctorial properties and β-sheet-rich secondary structure. Amyloid formation is a hallmark of many human diseases including Alzheimer's, Huntington's and the prion diseases. Therefore, understanding amyloidogenesis will provide insights into the development of therapeutics that target these debilitating diseases. A new class of 'functional' amyloids promises a unique glimpse at how nature has harnessed the amyloid fiber to accomplish important physiological tasks. Functional amyloids are produced by organisms spanning all aspects of cellular life. Herein we review amyloidogenesis, with special attention focused on the similarities and differences between the best characterized disease-associated amyloidogenic protein amyloid-β and the formation of several functional amyloids. The implications of studying functional amyloidogenesis and the strategies organisms employ to limit exposure to toxic intermediates will also be discussed.

Solution NMR structure of CsgE: Structural insights into a chaperone and regulator protein important for functional amyloid formation

“…The relationship between amyloid formation in vitro and amyloid diseases in vivo is not clear. Interestingly, functional amyloids have been identified in bacteria, fungi, insects, invertebrates, and humans, including a constituent of bacterial curli, fungi hydrophobins, and human Pmel17 in melanosomes (2,46,47). Functional amyloidogenesis in these systems requires tight regulation of the protein-protein interactions to avoid toxicity in the cell.…”

Aggregation and Prion-Like Properties of Misfolded Tumor Suppressors: Is Cancer a Prion Disease?

“…Although amyloid fibrils are typically associated with pathology, some amyloid fibrils perform biological functions. For instance, amyloid fibril formation by a domain of Pmel17 plays a role in melanin polymerization in animal cells, and some spider silk fibers consist of amyloid fibrils formed from spidroin (Chiti and Dobson 2006;Hammer et al 2008;Shewmaker et al 2011). Amyloid fibril formation has been shown for numerous proteins under the appropriate conditions; however, not all of these proteins are considered prion-like (Bucciantini et al 2002).…”

Thioflavin-S Staining of Bacterial Inclusion Bodies for the Fast, Simple, and Inexpensive Screening of Amyloid Aggregation Inhibitors

“…Amyloid structures have a core region formed by repetitive arrays of β-sheets oriented parallel to the fibril axis [1,4,5], and display similar biochemical, biophysical, tinctorial and morphological properties [6]. Even though amyloid aggregates can play specific physiological roles [1,7], in most cases they seem to be the root cause of a number of human diseases, the so-called amyloidoses, conformational diseases or protein misfolding disorders [1,6]. These include a broad range of disorders, from neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases or transmissible sporadic encephalopathies to non-neurodegenerative systemic and localized amyloidoses such as lysozyme and fibrinogen amyloidosis or type II diabetes and cataracts [8].…”