Dedifferenzierung von Astrozyten: Funktion bei Remyelinisierung induzierenden Prozessen
Zusammenfassung der Projektergebnisse
Protecting axons from degeneration represents a major need for the treatment of myelin disorders and especially the currently untreatable secondary progressive stages of multiple sclerosis (MS). Several lines of evidence indicate that remyelination represents one of the most effective means of achieving axonal protection. Remyelination can occur as a highly effective spontaneous regenerative process following demyelination. However, for reasons that have not been fully understood, this process is often incomplete or fails in MS. Many studies revealed an outstanding role of astrocytes as modulators of central nervous system regeneration. On the other hand, astrocytes might inhibit reparative processes in the brain. We are far away to understand this dual role of astrocytes. A better characterization of astrocyte function would allow a therapeutic manipulation of this important cell population and in consequence boost their pro-myelinating effects in the future. In this project we were able to show that (i) the fatty acid binding protein FABP7, also known as brain lipid binding protein (BLBP) is induced in activated astrocytes in two different MS animal models and in human MS lesions, (ii) that the presence of FABP7-expressing astrocytes temporally and spatially correlates with ongoing remyelination, (iii) that FABP7 regulates growth factor expression in astrocytes, (iiii) and that the fatty acid ω-3 docosahexaenoic acid (DHA), the major ligand of FABP7 augments remyelination in an experimental setting with impaired myelin repair. In summary, our findings suggest that FABP7 is an important factor for myelin repair and that DHA regulates remyelination and thus might be a novel therapeutic option to treat patient within the currently untreatable progressive disease stage. Underlying mechanisms as well as the potency of DHA to protect against axonal damage remains to be studied in future experiments.
Projektbezogene Publikationen (Auswahl)
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Brain Behav Immun. 2011 Nov;25(8):1554-68. Epub 2011 May 17
Kipp M, Gingele S, Pott F, Clarner T, van der Valk P, Denecke B, Gan L, Siffrin V, Zipp F, Dreher W, Baumgartner W, Pfeifenbring S, Godbout R, Amor S, Beyer C
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Endogeneous remyelination: findings in human studies. CNS Neurol Disord Drug Targets. 2012 Aug;11(5):598-609
Kipp M, Victor M, Martino G, Franklin RJ.
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Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions. Glia. 2012 Oct;60(10):1468-80. Epub 2012 Jun 11
Clarner T, Diederichs F, Berger K, Denecke B, Gan L, van der Valk P, Beyer C, Amor S, Kipp M
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Astrocytes regulate myelin clearance through recruitment of microglia during cuprizoneinduced demyelination.Brain. 2013 Jan;136(Pt 1):147-67
Skripuletz T, Hackstette D, Bauer K, Gudi V, Pul R, Voss E, Berger K, Kipp M, Baumgärtner W, Stangel M
