Abstract
Introduction. Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder, the primary pathological feature of which is the death of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of aggregated α-synuclein.
The objective of this review is to systematize current data on the molecular mechanisms of astrocyte involvement in the pathogenesis of PD, including disturbances in metabolic support, neurotransmitter metabolism, Ca2+ homeostasis, mitochondrial and lysosomal function, ferroptosis, neuroinflammation, and changes in the blood-brain barrier and glymphatic system, with an emphasis on genetic variants (LRRK2, GBA1, PARK7, SNCA, ATP13A2).
Material and methods. An analysis of original and review publications in PubMed, Scopus, Web of Science, and eLibrary for the period 2015–2025 was performed.
Results. In PD, astrocytes lose the ability to clear glutamate and α-synuclein, acquiring a reactive neurotoxic phenotype. MAO-B-dependent GABA and H2O2 synthesis, Ca2+ dysregulation, and mitochondrial dysfunction disrupt the neurotrophic support of dopaminergic neurons. Astrocyte-mediated ferroptosis mechanisms promote selective neuronal death. Genetic mutations associated with PD disrupt autophagy and lysosomal proteolysis and enhance the propagation of pathological α-synuclein. Astrocytes initiate and sustain neuroinflammation by influencing blood-brain barrier permeability and glymphatic system function.
Conclusion. Astrocytes are key mediators of non-cell-autonomous neurodegeneration in PD and a promising target for disease-modifying therapy. iPSC-derived astrocytes and midbrain organoids provide the basis for personalized disease modeling and drug screening aimed at correcting astrocytic dysfunction, normalizing intercellular interactions, and slowing PD progression.
Authors and affiliations
https://elibrary.ru/xehyba
L.G. Khaspekov (1), R.S. Mudarisova(1), N.A. Kolotyeva(1), A.B. Salmina(1), W. Li(2), S.N. Illarioshkin(1)
1-Russian Сenter of Neurology and Neurosciences, Volokolamskoe Highway, 80, Moscow, 125367, Russian Federation;
2-Health Sciences Institute, China Medical University, Puhe Rd, 77, Shenyang, 110122, China
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