The World of Functional Amyloid - The Functional Fold: Amyloid Structures in Nature - page 6

Amyloidogenic proteins are diverse in sequence and share few
characteristics—they are large and small, catalytic and structural,
abundant and sparse. It should be noted that relatively little is known
about mechanisms of amyloid formation in vivo . The mechanisms

of amyloid formation in vivo are likely to be different from what is

observed owing to the complex environmental conditions

(molecular crowding, chaperones, aggregases, disaggregases, etc.)
found inside living organisms.

in vitro

1. Amyloid as a Pathological Entity

Amyloid was discovered a century ago in the context of Alzheimer's
disease, which is characterized by neurodegeneration and extra-
cellular amyloid formation by the A

β

peptide. Subsequently, amyloid
has been associated with a wide variety of diseases including
Parkinson's, Huntington's, the prion diseases, and type II diabetes
(Table 1.1).

3

Table 1.1 Amyloid diseases

Amyloid forming protein Associated disease

Aβ precursor protein Alzheimer's disease

Prion protein Spongiform encephalopathies

Amylin Type II diabetes

Apolipoproteins Cardiac amyloidoses

Transthyretin Senile systemic amyloidosis

Cystatin C Familial dementia

Lactoferrrin Corneal amyloidosis

Immunoglobulin Myeloma-associated amyloidosis

Gelsolin Familial amyloidosis

Insulin Iatrogenic amyloidosis

β-Microglobulin Hemodialysis-associated amyloidosis

Lysozyme Familial amyloidosis

Lactadherin Senile aortic amyloidosis

Fibrinogen α-chain Familial amyloidosis

Amyloid diseases are characterized by the presence of fibrillar
amyloid deposits composed primarily of one amyloidogenic protein.
Genetic and pathological evidence suggest that amyloidogenesis