In neurodegenerative disorders such as Alzheimer's disease and multiple sclerosis, estrogen receptor beta (ERβ) seems to provide a protective anti-inflammatory response.
Here, we assessed the ability of DTI to distinguish between remyelination and neuroprotection following estrogen receptor β ligand (Indazole chloride, IndCl) treatment, which has been previously shown to stimulate functional remyelination, in the cuprizone (CPZ) diet mouse model of MS.
Therefore, we hypothesize that ERβ-selective agonists inhibit MHC II expression in microglia via inhibition of class II trans-activator (CIITA) expression by a mechanism involving inhibition of the translocation of IFNγ regulatory factor (IRF-1) to the nucleus, thereby inhibiting the inflammatory response and symptoms in the MS model.
Thus, the o-Methyl and o-Chloro IndCl analogues represent a class of ERβ ligands that offer significant remyelination and neuroprotection as well as modulation of the immune system; hence, they appear appropriate to consider further for therapeutic development in multiple sclerosis and other demyelinating diseases.