Janus faces of amyloid proteins in neuroinflammation
Open accessAbstract
Amyloid forming molecules are generally considered harmful. In Alzheimer's Disease two amyloid molecules Aβ A4 and tau vie for consideration as the main pathogenic culprit. But molecules obey the laws of chemistry and defy the way we categorize them as humans with our well-known proclivities to bias in our reasoning. We have been exploring the brains of multiple sclerosis patients to identify molecules that are associated with protection from inflammation and degeneration. In 2001 we noted that aB crystallin (cryab) was the most abundant transcript found in MS lesions, but not in healthy brains. Cryab can reverse paralysis and attenuate inflammation in several models of inflammation including experimental autoimmune encephalomyelitis (EAE), and various models of ischemia. Cryab is an amyloid forming molecule. We have identified a core structure common to many amyloids including amyloid protein Aβ A4, tau, amylin, prion protein, serum amyloid protein P, and cryab. The core hexapeptide structure is highly immune suppressive and can reverse paralysis in EAE when administered systemically. Administration of this amyloid forming hexapeptide quickly lowers inflammatory cytokines in plasma like IL-6 and IL-2. The hexapeptide bind a set of proinflammatory mediators in plasma, including acute phase reactants and complement components. The beneficial properties of amyloid forming hexapeptides provide a potential new therapeutic direction. These experiments indicate that amyloid forming molecules have Janus faces, providing unexpected benefit for neuroinflammatory conditions.
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Aβ has a physiological role in innate immunity.
“these studies highlight a physiological role for Aβ in innate immunity”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [143]
The Abstract reports that Aβ-derived peptides reduce inflammatory markers in experimental autoimmune encephalomyelitis and suggests that amyloid-forming proteins may contain inflammation in MS lesions. It does not establish a physiological role for Aβ in innate immunity; that extends the paper’s findings and its tentative account of a role in lesions. (LLM, conf=0.82)
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Self-citation
- Authors
- Steinman, L., Rothbard, J. B., & Kurnellas, M. P.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- Corresponding author
- Steinman, Lawrence
- Venue
- Journal of Clinical Immunology
- Published
- 2014-04-08
- Volume
- 34
- Issue
- S1
- Pages
- 61-63
- ISSN
- 0271-9142 (ISSN-L)
- 1573-2592
- PMC
- PMC5485228
- OpenAlex
- W2045457048
- Cited by
- 14
- References
- 15
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 1
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (T32AI007290)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- amyloid proteins, neuroinflammation, amyloid-beta, tau protein, alphaB-crystallin, multiple sclerosis, experimental autoimmune encephalomyelitis, hexapeptide, immunosuppression, complement system, acute phase proteins, neuroprotection, Alzheimer's disease, amylin, prion protein, serum amyloid P component, inflammatory cytokines
- MeSH terms
- Alzheimer Disease, Animals, Brain, Encephalomyelitis, Autoimmune, Experimental, Humans, Multiple Sclerosis, Interleukin-6, Neurogenic Inflammation, Mice, Amyloidogenic Proteins
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