Hyperactivity of the non-canonical inflammasome in SPG11 and SPG48.

ABSTRACT:

Background

Hereditary spastic paraplegia (HSP) denotes a heterogeneous group of neurodegenerative spastic gait disorders. Variants in SPG11 cause the most common autosomal recessive HSP also known as SPG11. The gene product Spatacsin interacts with the adaptor protein complex 5 (AP5). Because neurodegeneration in SPG11 is accompanied by marked neuro-inflammation, we hypothesised that Spatacsin may play a cell-autonomous role in pro-inflammatory cells.

Methods

Inflammasome activation was assessed in primary microglia and bone-marrow-derived-macrophages (BMDMs) from wild-type, Spg11, and Ap5z1 knockout (KO) mice and monocyte-derived-macrophages (MDMs) from patients with SPG11 mutations. Wild-type and Spg11 KO mice were used to study microglia activation and LPS-induced inflamm

SUBMITTER: Afzal MA 

PROVIDER: S-EPMC12595280 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature