Genomics

Dataset Information

0

Progranulin–glucocerebrosidase complex regulates tau and alpha-synuclein inclusions to alter phenotypes in tauopathy


ABSTRACT: Many neurodegenerative disorders including Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) are characterized by abnormal protein deposition and frequently show comorbid pathology. Progranulin (PGRN) is implicated not only in TDP-43 but in tau and alpha-synuclein proteinopathies. However, the underlying mechanisms are unknown. Here, we generated P301S tau transgenic mice with PGRN haploinsufficiency and loss and found that those mice exhibit exacerbated disinhibition phenotype while showing attenuated memory impairment, hippocampal atrophy, and transcriptomic changes. Remarkably, the phenotypic alteration was accompanied by an increase in tau inclusions, which are positive for alpha-synuclein, a PGRN binding partner beta-glucocerebrosidase (GCase), and its substrate glucosylceramide. GCase inhibition or PGRN deficiency enhanced tau aggregation induced by AD-derived tau seeds in neurons. In vitro, GCase and glucosylceramide promoted P301S tau aggregation. Similar co-pathology was observed in AD and FTLD-GRN patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE180672 | GEO | 2024/01/18

REPOSITORIES: GEO

Similar Datasets

2022-11-30 | GSE206368 | GEO
2023-02-03 | PXD033965 | Pride
2023-05-17 | GSE226624 | GEO
2020-10-20 | GSE153960 | GEO
2021-03-24 | GSE169478 | GEO
2023-12-08 | GSE242693 | GEO
2023-12-08 | GSE242180 | GEO
2019-06-23 | GSE118473 | GEO
2023-07-16 | GSE235515 | GEO
2022-02-03 | PXD028656 | Pride