Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a non-canonical neurotrophic factor broadly expressed throughout the brain. Previous work has shown that MANF modulates neuronal functions in various disease contexts; however, its cell-type-specific roles within the brain remain incompletely understood. Notably, clinical data link MANF deficiency to microcephaly in humans, yet traditional rodent models fail to replicate this pathology.
To address this discrepancy, researchers investigated the role of MANF in the brain by comparing mice and monkeys. Using CRISPR/Cas9 gene editing, they knocked down MANF both in vivo and in primary cell cultures. By integrating molecular biology, transcriptome sequencing, and functional rescue experiments, the team discovered that MANF is essential for astrocyte survival specifically in monkeys.
Key findings from the study include:
Collectively, this study underscores the significance of utilizing non-human primate models to investigate MANF neurobiology and to evaluate therapeutic strategies targeting MANF-related pathways. The work entitled “MANF is essential for astrocyte survival in the monkey brain” was published on Protein & Cell.
Protein & Cell
Experimental study
Not applicable
MANF is essential for astrocyte survival in the monkey brain