<i>In-situ</i> glial cell-surface proteomics identifies pro-longevity factors in <i>Drosophila</i>
Much focus has shifted towards understanding how glial dysfunction contributes to age-related neurodegeneration due to the critical roles glial cells play in maintaining brain health. Cell-cell interactions, which are largely mediated by cell-surface proteins, control many critical aspects of development and physiology; as such, dysregulation of glial cell-surface proteins is hypothesized to play…
Recent research has turned attention to the potential role of glial cell dysfunction in age-related neurodegeneration. Glial cells, which play a crucial role in maintaining brain health, interact with each other through cell-surface proteins. However, profiling these proteins in intact brains has been a challenging task. To tackle this issue, researchers have developed an in-situ cell-surface proteomic profiling method, which they applied to glial cells in the brains of intact fruit flies.
By comparing young and old flies, the study identified candidate genes that could be linked to brain aging. Through a genetic screen, one surface protein, DIP-β, emerged as a key player. DIP-β is down-regulated in older flies, but when overexpressed in adult glial cells, it has the potential to increase fly lifespan. The whole-head single-nucleus RNA-seq revealed that overexpression of DIP-β mainly affects glial and fat cells.
Furthermore, the research found that DIP-β overexpression in glial cells strengthens cell-cell communication, an important indicator of healthy brain function. This study marks the first application of in-situ cell-surface proteomics to glial cells in Drosophila and identifies DIP-β as a promising regulator of brain aging.
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