PMID: 22583440May 16, 2012Paper

Mechanisms in the development of multiple sclerosis lesions: reconciling autoimmune and neurodegenerative factors

CNS & Neurological Disorders Drug Targets
Johannes M van NoortSandra Amor

Abstract

Both immune-mediated and neurodegenerative processes play a role in the pathogenesis of multiple sclerosis (MS). There is still considerable debate, however, on how to link these two seemingly unrelated elements in disease. It has also remained unclear how the immune system can be involved without harboring any obvious myelin-directed abnormality in MS patients. Here, we propose that the unique properties of a small heat shock protein, HSPB5, can help reconcile the role of the immune system with the neurodegenerative element in MS, and explain the absence of any peripheral immune abnormality in patients. By being selectively induced as a protective stress protein in oligodendrocytes, and subsequently triggering activation of nearby microglia, HSPB5 accumulation translates neurodegenerative signals into a local innate immune response. The immune-regulatory profile of HSPB5-activated microglia, as well as animal model data, indicate that the HSPB5-induced innate response is neuroprotective. However, the presence of pro-inflammatory HSPB5-reactive memory T cells in the human immune repertoire, a unique feature among mammals, can subvert this response. Recruited by the innate response, such T cells respond to the accumulation of HS...Continue Reading

Citations

Mar 12, 2013·Antioxidants & Redox Signaling·Djordje Miljković, Ivan Spasojević
Oct 16, 2013·Journal of Neuroinflammation·Ganta Vijay ChaitanyaJonathan S Alexander
Jan 23, 2014·Journal of Neuroinflammation·Susana G Torres-PlatasNaguib Mechawar
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Aug 13, 2015·Multiple Sclerosis and Related Disorders·David Baker, Sandra Amor
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Jan 12, 2012·The International Journal of Biochemistry & Cell Biology·Johannes M van NoortSandra Amor
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Aug 19, 2020·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Zhe WangXiaoli Yu

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