Poly-γ-glutamic acid alleviates cytotoxicity and inflammation induced by pre-formed fibrils of α-synuclein in murine primary astrocytes

Poly-γ-glutamic acid (γ-PGA) is a bacterial-derived natural biopolymer that has gathered significant interest due to its antioxidant, anti-inflammatory, and neuroprotective properties. These characteristics make γ-PGA a potential candidate for the treatment of neurodegenerative diseases. In Parkinson's disease (PD), whose key pathological feature is the accumulation of neuronal α-synuclein aggregates, astrocytes, in addition to microglia, play a crucial role in clearing these aggregates; however, their capacity is limited. Overwhelmed astrocytes trigger an inflammatory response that exacerbates neurodegeneration. Therefore, strategies aimed at regulating the uptake of extracellular α-synuclein aggregates by astrocytes and mitigating inflammation could hold therapeutic promise. This work aimed to investigate the potential of γ-PGA in preventing or reversing the toxicity and inflammatory response induced by pre-formed α-synuclein fibrils (PFFs) in murine cortical astrocytes. Cell viability assays demonstrated that γ-PGA can counteract the toxicity induced by α-synuclein PFFs. Confocal microscopy and 3D reconstruction analyses revealed that γ-PGA colocalizes with PFFs, leading to a reduction in the uptake of these aggregates by astrocytes and a subsequent decrease in their inflammatory response. Consequently, γ-PGA emerges as a promising candidate for further investigation in the therapeutic management of PD.

Citation

Novello, C., Parati, M., Mazzetti, S. et al. (2025) Poly-γ-glutamic acid alleviates cytotoxicity and inflammation induced by pre-formed fibrils of α-synuclein in murine primary astrocytes. International Journal of Biological Macromolecules, 318(4), article number 145303.

Type

Journal article

Language

en

Description

This is an author's accepted manuscript of an article published by Elsevier on 19/06/2025, available at: https://doi.org/10.1016/j.ijbiomac.2025.145303 The accepted manuscript may differ from the final published version.

ISSN

0141-8130

EISSN

1879-0003

Collections

Faculty of Science and Engineering