ABHD8 is an α/β-hydrolase domain-containing protein that functions as a negative regulator of NLRP3 inflammasome activation by controlling NLRP3 protein turnover PMID:39225180. ABHD8 interacts physically with NLRP3 and acts as a scaffold that recruits the palmitoyltransferase ZDHHC12 to NLRP3, promoting NLRP3 palmitoylation and its subsequent degradation through the chaperone-mediated autophagy (CMA) pathway; loss of ABHD8 stabilizes NLRP3 and enhances inflammasome activation, whereas overexpression dampens LPS- and alum-triggered activation in vivo PMID:39225180. This regulatory axis is a target of viral subversion, as the SARS-CoV-2 nucleocapsid protein disrupts the ABHD8–NLRP3 association, elevating NLRP3 levels and driving excessive inflammasome activation PMID:39225180. ABHD8 expression is itself controlled at the 19p13.1 locus, where risk SNPs physically contact the ABHD8 promoter and risk alleles increase its transactivation PMID:27601076. Beyond these findings, the catalytic activity of the α/β-hydrolase domain and its direct enzymatic substrates have not been characterized in the available corpus.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2024 | Medium | ABHD8 interacts with NLRP3 and promotes its degradation through the chaperone-mediated autophagy (CMA) pathway; ABHD8 acts as a scaffold to recruit palmitoyltransferase ZDHHC12 to NLRP3, facilitating NLRP3 palmitoylation and subsequent CMA-mediated degradation. ABHD8 deficiency stabilizes NLRP3 protein and promotes inflammasome activation, while ABHD8 overexpression ameliorates LPS- or alum-triggered NLRP3 inflammasome activation in vivo. | PMID:39225180 | Autophagy |
| 2024 | Medium | The SARS-CoV-2 nucleocapsid (N) protein impairs the ABHD8-NLRP3 association, resulting in elevated NLRP3 protein levels and excessive inflammasome activation, placing ABHD8 as a target disrupted by viral infection. | PMID:39225180 | Autophagy |
| 2016 | Medium | Chromosome conformation capture identified physical interactions between four candidate risk SNPs at 19p13 and the ABHD8 locus; luciferase assays showed that six risk alleles increased transactivation of the ABHD8 promoter, and genotype-gene expression associations were identified for ABHD8 (P<2×10⁻³), indicating that multiple SNPs regulate ABHD8 expression. | PMID:27601076 | Nature Communications |