Thursday, 31 May 2018

Controlling Microglia


Inhibiting Hot microglia is what we think we want.

Loss of a molecule involved in growth factor signalling results in the formation of more microglia and worsening of inflammatory conditions. 

Some of you may be interested in this one

Voet S, Mc Guire C, Hagemeyer N, Martens A, Schroeder A, Wieghofer P, Daems C, Staszewski O, Walle LV, Jordao MJC, Sze M, Vikkula HK, Demeestere D, Van Imschoot G, Scott CL, Hoste E, Gonçalves A, Guilliams M, Lippens S, Libert C, Vandenbroucke RE, Kim KW, Jung S, Callaerts-Vegh Z, Callaerts P, de Wit J, Lamkanfi M, Prinz M, van Loo G. A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation. Nat Commun. 2018 May 23;9(1):2036.

Microglia, the mononuclear phagocytes of the central nervous system (CNS), are important for the maintenance of CNS homeostasis, but also critically contribute to CNS pathology. Here we demonstrate that the nuclear factor kappa B (NF-κB) regulatory protein A20 is crucial in regulating microglia activation during CNS homeostasis and pathology. In mice, deletion of A20 in microglia increases microglial cell number and affects microglial regulation of neuronal synaptic function. Administration of a sublethal dose of lipopolysaccharide induces massive microglia activation, neuroinflammation, and lethality in mice with microglia-confined A20 deficiency. Microglia A20 deficiency also exacerbates multiple sclerosis (MS)-like disease, due to hyperactivation of the Nlrp3 inflammasome leading to enhanced interleukin-1β secretion and CNS inflammation. Finally, we confirm a Nlrp3 inflammasome signature and IL-1β expression in brain and cerebrospinal fluid from MS patients. Collectively, these data reveal a critical role for A20 in the control of microglia activation and neuroinflammation

However, it does not show that if you augment the regulatory protein it inhibits disease.

Likewise there are other studies showing if you remove this molecule from B cells you get autoantibodies but it makes  severe defects in B-cell development and differentiation.

Nuclear factor Kappa B is a critical molecule involved in inflammation and targeting this probably is of value as a number of MS drugs do this. However there will be consequences of  this and so whether this is a useful druggable target remains to be seen 

1 comment:

  1. In this study they fond microglia is help myelination

    Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells

    https://elifesciences.org/articles/33385?utm_source=content_alert&utm_medium=email&utm_content=fulltext&utm_campaign=5-June-18-elife-alert

    Obrigado

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