Download CONFERENCE REPORT FROM A NOBEL MINISYMPOSIUM/JIM

CONFERENCE REPORT FROM A
NOBEL MINISYMPOSIUM/JIM SYMPOSIUM
Amyloid – a multifaceted player in human health and disease.
Guest Editor: Jan Johansson
Stockholm, Sweden
The meeting
The Minisymposium “Amyloid – a multifaceted player in human health and
disease” was held in Nobel Forum at Karolinska Institutet, Stockholm on
June 10-11th 2015. The Minisymposium is part of the series “Frontiers in
Medicine” arranged by the Nobel assembly at Karolinska Institutet since
1949, with the aim to highlight topics of immediate medical relevance and
that bridge preclinical and clinical areas.
Co-Support Nobel assembly and Journal of Internal Medicine
This Minisymposium was co-supported by the Nobel assembly at Karolinska
Institutet and the Journal of Internal Medicine and attracted academic
scientists as well researchers from biotech and pharmceutical companies.
The topic
The aim of this Minisymposium was to bring together researchers who work
on amyloid in a broad perspective. This is motivated by recent discoveries
showing that amyloid is intricately related not only to traditional amyloid
diseases like Alzheimer’s disease and transmissible spongiform
encephalopathies, but is also involved in a broad spectrum of human health
topics, including infectious diseases and the innate defense thereof, the
issue of amyloid transmissibility in relation to human food safety and the
emerging use of amyloid-like biomaterials for regenerative medicine.
Some amyloid diseases, like Alzheimer’s disease and type II diabetes
mellitus, constitute major medical and socioeconomic challenges, but
amyloid-like structures have also been described in high-performance fibers
like spider silk, as well as in secretory granules and in the pigment
epithelium of the eye.
The presentations
The minisymposium had four sessions entitled amyloid biology,
transmissible amyloid, amyloid and defense mechanisms and treatment of
amyloid diseases. In an amyloid fiber, one specific protein builds β-sheet
polymers where the same interactions are seen over and over again in a
highly repetitive manner.
Proteins and peptides of many sequences have been observed to change from
their native structures into amyloid fibrils, and in line with those
observations almost all proteins apparently contain segments with the
potential to form amyloid-like fibrils.
However, only a tiny fraction of all proteins really forms amyloid - so far only
30 amyloid diseases have been described, suggesting that Nature has found
ways to prevent aggregation into amyloid for the main part of the proteome.
Possible protective mechanisms are mediated by general molecular
chaperones, but more client-specific chaperones like the BRICHOS domain
may confer specific protection against amyloid. These novel findings may
explain why amyloid diseases are rare in spite of the fact that almost any
protein can form amyloid.
Amyloid structures are apparently involved in host-pathogen interactions in
a multi-faceted manner. The HIV virus uses amyloid fibrils (called SEVI) of
an interior segment of prostatic acidic phosphatase present in semen to
vastly increase its infectivity. The physiological function of SEVI is probably
in sperm quality control, and the viral hijacking of amyloid fibrils may be
important in sexual transmission of HIV infection and could represent a
target for its prevention. On the other hand, bacterial curli fibers, that
mediate attachment, are built from amyloid-like structures, the human
antimicrobial peptide LL37 can reduce infectivity of uropathogenic E. coli by
preventing curli formation, and the human antimicrobial peptide α-defensin
6 forms nanonets with amyloid-like properties, and thereby entangles
invading bacteria into aggregates. These recent discoveries elegantly show
that amyloid is harnessed both by pathogens and by the innate immune
system, and that amyloid can be central in the fight between invaders and
protective systems.
It is established that the prion disease BSE (bovine spongiform
encephalopathy) can spread to humans by oral intake. Prion diseases like
kuru, Creutzfeldt-Jakob diseases, and scrapie, can all be transmitted to
monkeys via the food chain. The prion protein seeding phenomenon is
beginning to be understood at a molecular level, but self-propagation of
pathogenic protein aggregates appears to be a unifying common principle for
several neurodegenerative diseases, including Alzheimer’s and Parkinson's
diseases. It has been shown that two different systemic amyloidosis, AA and
apolipoprotein AII, are transmissible in mice, and cheetahs in captivity often
suffer from AA amyloidosis that probably spreads via faeces
Conclusion
Finally, fibrils of one protein can seed other proteins into amyloid fibrils (eg
Aβ can seed islet polypeptide amyloid formation) and, even in vivo, several
different amyloidogenic proteins, including peptides designed to form
nanomaterials, have been shown to seed AA amyloidosis in a mouse model.
The cross-seeding phenomenon is thus of potential great importance in
relation to ongoing work to use amyloid-like biomaterials in human
medicine, eg for tissue engineering and drug delivery.
Articles and more about the Journal of Internal Medicine at www.jim.se