Astrocyte Endfeet in Brain Function and Pathology: Open Questions

Astrocyte endfeet enwrap the entire vascular tree within the central nervous system, where they perform important functions in regulating the blood-brain barrier (BBB), cerebral blood flow, nutrient uptake, and waste clearance. Accordingly, astrocyte endfeet contain specialized organelles and proteins, including local protein translation machinery and highly organized scaffold proteins, which anchor channels, transporters, receptors, and enzymes critical for astrocyte-vascular interactions. Many neurological diseases are characterized by the loss of polarization of specific endfoot proteins, vascular dysregulation, BBB disruption, altered waste clearance, or, in extreme cases, loss of endfoot coverage. A role for astrocyte endfeet has been demonstrated or postulated in many of these conditions. This review provides an overview of the development, composition, function, and pathological changes of astrocyte endfeet and highlights the gaps in our knowledge that future research should address.

Automated summary

Astrocyte endfeet surround the entire vascular tree in the central nervous system and play important roles in regulating the blood-brain barrier, cerebral blood flow, nutrient uptake, and waste clearance. They contain specialized organelles and proteins necessary for astrocyte-vascular interactions. Many neurological diseases are associated with abnormalities in astrocyte endfeet, including loss of protein polarization, vascular dysregulation, and disruption of the blood-brain barrier. This review provides an overview of astrocyte endfeet and highlights the need for future research to address gaps in our understanding.