New possible molecular target: VRAC Current 1

[frodo]

A Virus-Induced Gliopathy?

In this issue of Neurology® Neuroimmunology & Neuroinflammation, Dahl et al.3 report that antibodies to membrane protein modulator of VRAC current 1 (MLC1) may be associated with MS pathology.

https://www.neurology.org/doi/full/10.1 ... 0000200383

MLC1 is a membrane protein primarily located at astrocyte junctions.4 Notably, GlialCAM is a known binding partner of MLC1,5 and sequence variants in the genes of either are associated with a childhood leukodystrophy known as megalencephalic leukoencephalopathy with subcortical cysts (MLC)

While the sequence of events remains elusive, it is intriguing to speculate that EBV infection leads to generation of anti-EBNA1 antibodies (which is increased further in the presence of HLA-DRB1*15:01) to cross-react against several different CNS autoantigens. Targeting of GlialCAM could result in a secondary reactivity to MLC1, through a process known as intermolecular antigenic spreading, whereby proteins in a neighboring region of immune attack are also attacked in what might be considered collateral damage

Modulator of VRAC Current 1 Is a Potential Target Antigen in Multiple Sclerosis

https://www.neurology.org/doi/full/10.1 ... 0000200374

Results

Our results corroborate the existing concept of a highly diverse autoimmune response in MS. Yet, a significantly elevated antibody response against the membrane protein modulator of VRAC current 1 (MLC1) was noted in B-cell culture supernatants and serum samples of patients with MS. Furthermore, significantly elevated titers to MLC1 were observed in the CSF of patients with neuroinflammatory diseases other than MS. Neurons and astrocytes were identified as the main cell types expressing MLC1 in the brain of a patient with MS. Injection of anti-MLC1 antibodies into mice with EAE led to strong in vivo binding to cerebral cortical neurons and to the death of 4 of the 7 injected mice.