Emerging Role of Extracellular Vesicles in Intercellular Communication in the Brain: Implications for Neurodegenerative Diseases and Therapeutics

Sarkar, Souhrid; Patranabis, Somi

doi:10.1007/s12013-024-01221-z

Cited by 8 publications

(1 citation statement)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fatal communication between immune cells, both glial cells and macrophages, and MNs in determining inflammatory status involves transcellular signalling through chemical molecules. More and more evidence indicates extracellular vesicles as a new and promising way of cell-to-cell communication in the CNS [ 21 ]. Unfortunately, to date, very little data on the role of peripheral macrophages in contributing to MNs degeneration is present, whereas the majority of research focuses on the role of microglia.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles from NSC-34 MN-like Cells Transfected with Mutant SOD1 Modulate Inflammatory Status of Raw 264.7 Macrophages

Carata,

Muci,

Mariano

et al. 2024

Genes

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting the brain and spinal cord. Non-neuronal cells, including macrophages, may contribute to the disruption of motor neurons (MNs), neuromuscular junction dismantling and clinical signs of ALS. Understanding the modality and the effect of MNs–macrophage communication is pivotal. Here, we focus on extracellular vesicle (EVS)-mediated communication and, in particular, we analyze the response of macrophages. NSC-34 cells transfected with mutant SOD1 (G93A, A4V, G85R, G37R) and differentiated towards MN-like cells, and Raw 264.7 macrophages are the cellular models of the study. mSOD1 NSC-34 cells release a high number of vesicles, both large-lEVs (300 nm diameter) and small-sEVs (90 nm diameter), containing inflammation-modulating molecules, and are efficiently taken up by macrophages. RT-PCR analysis of inflammation mediators demonstrated that the conditioned medium of mSOD1 NSC-34 cells polarizes Raw 264.7 macrophages towards both pro-inflammatory and anti-inflammatory phenotypes. sEVs act on macrophages in a time-dependent manner: an anti-inflammatory response mediated by TGFβ firstly starts (12 h); successively, the response shifts towards a pro-inflammation IL-1β-mediated (48 h). The response of macrophages is strictly dependent on the SOD1 mutation type. The results suggest that EVs impact physiological and behavioral macrophage processes and are of potential relevance to MN degeneration.

show abstract

Section: Discussionmentioning

confidence: 99%