Serum amyloid A and protein AA: Molecular mechanisms of a transmissible amyloidosis

Westermark, Gunilla T.; Westermark, Per

doi:10.1016/j.febslet.2009.04.026

Cited by 84 publications

(75 citation statements)

References 66 publications

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“…AA amyloidosis can be induced in mice by administering extracts of amyloid-laden tissue that act as an amyloid enhancing factor (43,44), and the disease has been shown to propagate via a prion-like mechanism (45). More recently, SAA oligomers have been identified as the species that triggers and transmits AA amyloidosis in mice (30,31).…”

Section: Discussionmentioning

confidence: 99%

Pathogenic Serum Amyloid A 1.1 Shows a Long Oligomer-rich Fibrillation Lag Phase Contrary to the Highly Amyloidogenic Non-pathogenic SAA2.2

Srinivasan

Patke

Wang

et al. 2013

Journal of Biological Chemistry

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Background: Murine SAA1.1 is pathogenic and SAA2.2 is non-pathogenic in AA amyloidosis. Results: SAA1.1 and SAA2.2 exhibit different biophysical properties, including fibrillation kinetics and fibril morphology. Conclusion:The distinct biophysical properties of highly homologous SAA proteins may contribute to their different pathogenicity during chronic inflammation. Significance: Structural and kinetic factors, more than their intrinsic amyloidogenicity, may determine the diverse pathogenicity among nearly identical SAA isoforms.

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Section: Discussionmentioning

confidence: 99%

Pathogenic Serum Amyloid A 1.1 Shows a Long Oligomer-rich Fibrillation Lag Phase Contrary to the Highly Amyloidogenic Non-pathogenic SAA2.2

Srinivasan

Patke

Wang

et al. 2013

Journal of Biological Chemistry

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“…The systemic amyloidosis, amyloid A (AA) amyloidosis, occurs in response to chronic inflammation when AA, a ~76 amino acid N-terminal fragment of serum amyloid A protein, forms amyloid conformers that are deposited in various tissues including the spleen, liver and kidneys (Westermark and Westermark, 2009). Parenteral or oral administration of AA fibers purified from the liver of mice with AA amyloidosis is sufficient to accelerate AA amyloidosis in response to inflammatory stress (Lundmark et al, 2002).…”

Section: Amyloid a Amyloidosismentioning

confidence: 99%

Prion-like disorders: blurring the divide between transmissibility and infectivity

Cushman

Johnson

King

et al. 2010

Journal of Cell Science

266

351

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SummaryPrions are proteins that access self-templating amyloid forms, which confer phenotypic changes that can spread from individual to individual within or between species. These infectious phenotypes can be beneficial, as with yeast prions, or deleterious, as with mammalian prions that transmit spongiform encephalopathies. However, the ability to form self-templating amyloid is not unique to prion proteins. Diverse polypeptides that tend to populate intrinsically unfolded states also form self-templating amyloid conformers that are associated with devastating neurodegenerative disorders. Moreover, two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins. Can these proteins and the neurodegenerative diseases to which they are linked become 'infectious' too? Here, we highlight advances that define the transmissibility of amyloid forms connected with Alzheimer's disease, Parkinson's disease and Huntington's disease. Collectively, these findings suggest that amyloid conformers can spread from cell to cell within the brains of afflicted individuals, thereby spreading the specific neurodegenerative phenotypes distinctive to the protein being converted to amyloid. Importantly, this transmissibility mandates a re-evaluation of emerging neuronal graft and stem-cell therapies. In this Commentary, we suggest how these treatments might be optimized to overcome the transmissible conformers that confer neurodegeneration.Key words: Amyloid, Infectivity, Prion, Stem cell, Therapy, Transmissibility Journal of Cell Science1192 to familial forms of GSS (Hsiao et al., 1989), FFI (Medori et al., 1992) and CJD (Goldgaber et al., 1989). Moreover, in mice, an FFI-linked mutation in PrP can induce neurodegenerative disease and spontaneous generation of infectious material . At the other extreme, missense mutations in PrP can confer resistance to prion disease (Mead et al., 2009). Importantly, PrPknockout mice resist infection by exogenous TSE-inducing prions (Bueler et al., 1993). This resistance arises because the infectious form of PrP must recruit and convert endogenous PrP to transmit disease. Indeed, if PrP-expressing neurons are grafted into PrPknockout mice, then only the grafts become infected upon prion exposure, whereas surrounding tissue is unperturbed (Brandner et al., 1996). This experimental observation might prove to be pivotal for devising strategies to mitigate the transmissibility of other human neurodegenerative disease proteins.The cascade of amyloid seeding incited by prions, however, is not always problematic and is certainly not restricted to mammals. In yeast, several proteins form prions that confer specific heritable phenotypes, which are either benign or advantageous under diverse environmental conditions (Alberti et al., 2009;Shorter and Lindquist, 2005;True and Lindquist, 2000;Tyedmers et al., 2008). These specific heritable phenotypes can be induced de novo by the infecti...

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“…1C). To examine the binding of HS/heparin to the lipoproteins, we incubated HDL and HDL-SAA with 3 H-labeled polysaccharide. The amounts of 3 H-labeled HS/heparin bound to the particles were analyzed using a nitrocellulose filter trapping method (27).…”

Section: Hs/heparinmentioning

confidence: 99%

“…During longstanding inflammatory conditions, SAA can accumulate as deposits in organs, primarily in the spleen, liver, and kidneys, causing inflammation-related (AA) amyloidosis (3,4). The development of the disease is a progressive process, often associated with persistent or reoccurring acute inflammation such as rheumatoid arthritis and familial Mediterranean fever (5).…”

mentioning

confidence: 99%

Heparan Sulfate Dissociates Serum Amyloid A (SAA) from Acute-phase High-density Lipoprotein, Promoting SAA Aggregation

Noborn

Ancsin

Ubhayasekera

et al. 2012

Journal of Biological Chemistry

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Background: Serum amyloid A (SAA) is normally associated with the high-density lipoprotein (HDL). Results: Heparan sulfate (HS) dissociates SAA from HDL, leading to AA amyloidosis. The activity requires a minimum length of 12-14 sugar units. Conclusion:The result proposes an explanation for the findings that short HS precludes AA amyloidosis. Significance: This study defines a novel role for HS in AA amyloidosis.

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Serum amyloid A and protein AA: Molecular mechanisms of a transmissible amyloidosis

Cited by 84 publications

References 66 publications

Pathogenic Serum Amyloid A 1.1 Shows a Long Oligomer-rich Fibrillation Lag Phase Contrary to the Highly Amyloidogenic Non-pathogenic SAA2.2

Pathogenic Serum Amyloid A 1.1 Shows a Long Oligomer-rich Fibrillation Lag Phase Contrary to the Highly Amyloidogenic Non-pathogenic SAA2.2

Prion-like disorders: blurring the divide between transmissibility and infectivity

Heparan Sulfate Dissociates Serum Amyloid A (SAA) from Acute-phase High-density Lipoprotein, Promoting SAA Aggregation

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