Figure 8 | Scientific Reports

Figure 8

From: Connecting Neuronal Cell Protective Pathways and Drug Combinations in a Huntington’s Disease Model through the Application of Quantitative Systems Pharmacology

Figure 8The alternative text for this image may have been generated using AI.

Ethoxzolamide may not work through the canonical carbonic anhydrase mechanism. The methyl sulfonyl analog of ETX does not contain the sulfonamide group of ETX and it is not expected to inhibit carbonic anhydrase29, though we did not test this directly. This analog is 7-fold more potent than ETX in protecting STHdh Q111 cells from stress induced cell death in the propidium iodide assay suggesting that the mechanism of protection of ETX is not through carbonic anhydrase inhibition. Acetazolamide, brinzolamide and dorzolamide, all reported carbonic anhydride inhibitors, did not protect STHdh Q111 cells (see Supplementary Figure S8) further supporting the idea that inhibition of carbonic anhydrase is not a protective mechanism. Interestingly, the methyl sulfonyl analog only protected ~50% of the STHdh Q111 cells consistent with the existence of distinct protection mechanisms in different subpopulations of cells.

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