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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