The World of Functional Amyloid - The Functional Fold: Amyloid Structures in Nature - page 10

1. Challenges and Future Directions

Although pathological amyloid was discovered over 100 years ago,
the concept of functional amyloid is about 10 years old. In fact, only
a handful of examples exist at this point. Since amyloid can fulfil a
variety of functions and has, apparently, been conserved in evolution,
it is likely that many more examples of functional amyloid exist.
However, amyloid is a somewhat heterogenous mesoscale structure,
making it difficult to detect and classify, particularly at the sub-cellular
level. A central challenge for the field of functional amyloid is the
development of an effective, high-throughput method for identifying
more examples of functional amyloid. Imaging advances could
offer such a solution, especially if amyloid-specific conformational
antibodies prove robust. Identification of highly amyloidogenic
polypeptide sequences using bioinformatics approaches could also
guide

investigations.
In addition to gaining insight into biology, the study of
functional amyloid could lead to profound advances in medicine
and nanomaterials (see chapter 10, this volume). Amyloid-related
diseases, including Alzheimer's and Parkinson's, affect millions of
people and are presently untreatable. A better understanding of
how organisms regulate functional amyloid to prevent toxicity could
point the way to treatments for these important neurodegenerative
diseases. For example, recent evidence suggests that cells may
contain generalized pathways for creating and removing amyloid-
like aggregates.

in vivo

54

Pharmacological control of endogenous systems
for regulating the formation and degradation of amyloid could prove
extremely useful in treating amyloid-associated diseases.

55
Amyloid has remarkable mechanical and biochemical properties,
exhibiting resistance to chemical denaturation and protease
degradation as well as strength comparable to steel.

56,57

Many
organisms have made use of these properties to effect a variety of
biological processes; this suggests the possibility of using amyloid
as a biomaterial. For example, spider silk, which likely contains
amyloid-like motifs, has exceptional strength but is currently
difficult to produce on industrial scales. A deeper understanding of
how organisms manufacture amyloid could lead to the development
of remarkably strong and light biomaterials.
In conclusion, amyloid appears to be an ancient, evolutionarily con-
served structural motif or quaternary structure with an important