This paper below demonstrates that it is not only monocytes that phagocytes beta-amyloid but also astrocytes do the same. Extracellular ATP improves the phagocyting of astrocytes and most likely extra ATP also improves the function of monocytes.

It looks more and more that AD is a lack of energy disease. ATH434 improves energy supply as the posters by Kosman et al have demonstrated (https://alteritytherapeutics.com/wp-content/uploads/DB-sfn-2024-poster-10Oct24.pdf) in his seahorse metabolic analyses.

Purinergic Signal

. 2025 Jan 21.

doi: 10.1007/s11302-025-10066-x. Online ahead of print.

Extracellular ATP regulates phagocytic activity, mitochondrial respiration, and cytokine secretion of human astrocytic cells

Sijie Shirley Yang ¹, Noah A H Brooks ¹, Dylan E Da Silva ², Julien Gibon ¹, Hashim Islam ³, Andis Klegeris ⁴

Affiliations Expand

• PMID: 39833586

DOI: 10.1007/s11302-025-10066-x

Abstract

The two main glial cell types of the central nervous system (CNS), astrocytes and microglia, are responsible for neuroimmune homeostasis. Recent evidence indicates astrocytes can participate in removal of pathological structures by becoming phagocytic under conditions of neurodegenerative disease when microglia, the professional phagocytes, are impaired. We hypothesized that adenosine triphosphate (ATP), which acts as damage-associated molecular pattern (DAMP), when released at high concentrations into extracellular space, upregulates phagocytic activity of human astrocytes. This study is the first to measure changes in phagocytic activity and mitochondrial respiration of human astrocytic cells in response to extracellular ATP. We demonstrate that ATP-induced phagocytic activity of U118 MG astrocytic cells is accompanied by upregulated mitochondrial oxidative phosphorylation, which likely supports this energy-dependent process. Application of a selective antagonist A438079 provides evidence identifying astrocytic purinergic P2X7 receptor (P2X7R) as the potential regulator of their phagocytic function. We also report a rapid ATP-induced increase in intracellular calcium ([Ca²⁺]_i), which could serve as regulator of both the phagocytic activity and mitochondrial metabolism, but this hypothesis will need to be tested in future studies. Since ATP upregulates interleukin (IL)-8 secretion by astrocytes but has no effect on their cytotoxicity towards neuronal cells, we conclude that extracellular ATP affects only specific functions of astrocytes. The selectivity of P2X7R-dependent regulation of astrocyte functions by extracellular ATP could allow targeting this receptor-ligand interaction to upregulate their phagocytic function. This could have beneficial outcomes in neurodegenerative disorders, such as Alzheimer's disease, that are characterized by reactive astrocytes and defective phagocytic processes.