10 juillet 2017

Facteur inhibiteur de la migration des macrophages: une cytokine multifacette impliquée dans de multiples maladies neurologiques

Aperçu: G.M.
Le facteur inhibiteur de la migration des macrophages (MIF) est une cytokine.
La MIF joue un rôle important dans la promotion des processus tumoraux, la maladie d'Alzheimer, et est également sur-régulée dans les "troubles du spectre de l'autisme" et la lésion de la moelle épinière, ce qui contribue à la gravité de la zone lésée. L'effet protecteur de la MIF a été signalé dans la sclérose latérale amyotrophique par sa réduction de la SOD1 agrégée mal repliée , réduisant ainsi la gravité de cette maladie. Fait intéressant, un rôle protecteur et pathologique pour le MIF a été impliqué dans l'accident vasculaire cérébral et l'ischémie cérébrale, ainsi que dans la dépression. Ainsi, le rôle de la MIF dans les troubles neurologiques semble être diversifié avec des effets bénéfiques et adversaires.  

Exp Neurol. 2017 Jul 2. pii: S0014-4886(17)30160-7. doi: 10.1016/j.expneurol.2017.06.021.

Macrophage migration inhibitory factor: A multifaceted cytokine implicated in multiple neurological diseases

Author information

1
Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel.
2
Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel; The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel. Electronic address: adriani@bgu.ac.il.

Abstract

Macrophage migration inhibitory factor (MIF) is a conserved cytokine found as a homotrimer protein. It is found in a wide spectrum of cell types in the body including neuronal and non-neuronal cells. MIF is implicated in several biological processes; chemo-attraction, cytokine activity, and receptor binding, among other functions. More recently, a chaperone-like activity has been added to its repertoire. In this review, we focus on the implication of MIF in the central nervous system and peripheries, its role in neurological disorders, and the mechanisms by which MIF is regulated. Numerous studies have associated MIF with various disease settings. MIF plays an important role in advocating tumorigenic processes, Alzheimer's disease, and is also upregulated in autism-spectrum disorders and spinal cord injury where it contributes to the severity of the injured area. The protective effect of MIF has been reported in amyotrophic lateral sclerosis by its reduction of aggregated misfolded SOD1, subsequently reducing the severity of this disease. Interestingly, a protective as well as pathological role for MIF has been implicated in stroke and cerebral ischemia, as well as depression. Thus, the role of MIF in neurological disorders appears to be diverse with both beneficial and adversary effects. Furthermore, its modulation is rather complex and it is regulated by different proteins, either on a molecular or protein level. This complexity might be dependent on the pathophysiological context and/or cellular microenvironment. Hence, further clarification of its diverse roles in neurological pathologies is warranted to provide new mechanistic insights which may lead in the future to the development of therapeutic strategies based on MIF, to fight some of these neurological disorders.

KEYWORDS:

Central nervous system; MIF; Neurodegeneration; Neurological diseases

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