The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum-microglia crosstalk preventing disease progression in a mouse model of Huntington's disease.

ABSTRACT: The longevity-associated variant (LAV) of the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been found significantly enriched in long-living individuals. Neuroinflammation is a key player in Huntington's disease (HD), a neurodegenerative disorder caused by neural death due to expanded CAG repeats encoding a long polyglutamine tract in the huntingtin protein (Htt). Herein, we showed that striatal-derived cell lines with expanded Htt (STHdh Q^111/111) expressed and secreted lower levels of BPIFB4, when compared with Htt expressing cells (STHdh Q^7/7), which correlated with a defective stress response to proteasome inhibition. Overexpression of LAV-BPIFB4 in STHdh Q^111/111 cells was able to rescue both the BPIFB4 secretory p

SUBMITTER: Di Pardo A 

PROVIDER: S-EPMC7368858 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature