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

Cell Death & Disease
Alba Di PardoAnnibale Alessandro Puca

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 Q111/111) expressed and secreted lower levels of BPIFB4, when compared with Htt expressing cells (STHdh Q7/7), which correlated with a defective stress response to proteasome inhibition. Overexpression of LAV-BPIFB4 in STHdh Q111/111 cells was able to rescue both the BPIFB4 secretory profile and the proliferative/survival response. According to a well-established immunomodulatory role of LAV-BPIFB4, conditioned media from LAV-BPIFB4-overexpressing STHdh Q111/111 cells were able to educate Immortalized Human Microglia-SV40 microglial cells. While STHdh Q111/111 dying cells were ineffective to induce a CD163 + IL-10high pro-resolving microglia compared to normal STHdh Q7/7, LAV-BPIFB4 transduction promptly restored the central immune control through a mechan...Continue Reading

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Citations

Oct 2, 2020·International Journal of Molecular Sciences·Marta DossenaAnnibale Alessandro Puca
Aug 17, 2021·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Elena CiagliaAnnibale Alessandro Puca

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Datasets Mentioned

BETA
GM26793

Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
FACS
RNAseq
PCR
transfection
flow cytometry
transgenic
FCS

Clinical Trials Mentioned

NCT02215616

Software Mentioned

LEGENDplex
G Power
ImageJ
FeatureCount
GraphPad
Ensembl
TapeStation
EdgeR
Panther
Fastq

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