Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates

• Published in: Journal of neuroinflammation 2021-06, Vol.18 (1), p.124-124, Article 124
• Main Authors: Rostami, Jinar, Mothes, Tobias, Kolahdouzan, Mahshad, Eriksson, Olle, Moslem, Mohsen, Bergström, Joakim, Ingelsson, Martin, O'Callaghan, Paul, Healy, Luke M, Falk, Anna, Erlandsson, Anna
• Format: Article
• Language: English
• Subjects: alpha-Synuclein; alpha-Synuclein - metabolism; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amino acids; Amyloid beta-Peptides - metabolism; Amyloid-beta; Amyloid-β; Astrocyte; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Brain - metabolism; Cell culture; Cell Membrane Structures - physiology; Cell membranes; Cells, Cultured; Co-culture; Coculture Techniques; Crosstalk; Degradation; Enzyme-linked immunosorbent assay; Experiments; Fibrils; Growth factors; Humans; Immunocytochemistry; Induced Pluripotent Stem Cells; Inflammation; Insulin; Intracellular; Medicin och hälsovetenskap; Microglia; Microglia - metabolism; Microglia - pathology; Microscopy, Confocal; Movement disorders; Nanotubes; Neurodegenerative diseases; Neuroimaging; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Pathology; Pluripotency; Protein Aggregates; Protein Aggregation, Pathological; Proteins; Proteolysis; Synuclein; Tunneling nanotube; α-Synuclein
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-021-02158-3

Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by brain accumulation of aggregated amyloid-beta (Aβ) and alpha-synuclein (αSYN), respectively. In order to develop effective therapies, it is crucial to understand how the Aβ/αSYN aggregates can be cleared. Compelling data indicate that neuroinflammatory cells, including astrocytes and microglia, play a central role in the pathogenesis of AD and PD. However, how the interplay between the two cell types affects their clearing capacity and consequently the disease progression remains unclear. The aim of the present study was to investigate in which way glial crosstalk influences αSYN and Aβ pathology, focusing on accumulation and degradation. For this purpose, human-induced pluripotent cell (hiPSC)-derived astrocytes and microglia were exposed to sonicated fibrils of αSYN or Aβ and analyzed over time. The capacity of the two cell types to clear extracellular and intracellular protein aggregates when either cultured separately or in co-culture was studied using immunocytochemistry and ELISA. Moreover, the capacity of cells to interact with and process protein aggregates was tracked using time-lapse microscopy and a customized "close-culture" chamber, in which the apical surfaces of astrocyte and microglia monocultures were separated by a