Dataset Information


An anti-CAPN5 intracellular antibody acts as an inhibitor of CAPN5-mediated neuronal degeneration.

ABSTRACT: CAPN5 has been linked to autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV). Activation of CAPN5 may increase proteolysis and degradation of a wide range of substrates to induce degeneration in the retina and the nerve system. Thus, we developed an inhibitory intracellular single chain variable fragment (scFv) against CAPN5 as a potential way to rescue degeneration in ADNIV disease or in neuronal degeneration. We report that overexpression CAPN5 increases the levels of the auto-inflammatory factors toll like receptor 4 (TLR4), interleukin 1 alpha (IL1alpha), tumor necrosis factor alpha (TNFalpha) and activated caspase 3 in 661W photoreceptor-like cells and SHSY5Y neuronal-like cells. Both C4 and C8 scFvs specifically recognize human/mouse CAPN5 in 661W cells and SHSY5Y cells, moreover, both the C4 and C8 scFvs protected cells from CAPN5-induced apoptosis by reducing the levels of activated caspase 3 and caspase 9. The cellular expression C4 scFv reduced levels of the pro-inflammatory factor IL1-alpha activated caspase 3 in cells after CAPN5 overexpression. We suggest that CAPN5 expression has important functional consequences in auto-inflammatory processes, and apoptosis in photoreceptor like cells and neural-like cells. Importantly, the specific intracellular targeting of antibody fragments blocking activation of CAPN5 act as inhibitors of CAPN5 functions in neural like cells, thus, our data provides a novel potential tool for therapy in CAPN5-mediated ADNIV or neurodegenerative diseases.

PROVIDER: S-EPMC5725022 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC4169796 | BioStudies
| S-EPMC3990166 | BioStudies
| S-EPMC6054427 | BioStudies
| S-EPMC4391918 | BioStudies
| S-EPMC7173350 | BioStudies
| S-EPMC4512628 | BioStudies
| S-EPMC7132063 | BioStudies
| S-EPMC6527583 | BioStudies
| S-EPMC3464205 | BioStudies
| S-EPMC7493429 | BioStudies