Functional characteristics, intercellular interactions and pathophysiological associations of astrocytes in...

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, and its incidence rate is increasing at an alarming rate. Astrocytes exhibit a complex array of functions that play a critical role in the pathogenesis and progression of PD. These multifaceted functions substantially influence disease development and exacerbation. Although numerous studies have investigated the role of astrocytes in PD, the interactions between astrocytes and other cellular or molecular factors during the course of neurological deterioration in PD have not been comprehensively characterized. Therefore, this review aims to highlight the roles and functional characteristics of astrocytes in PD. Astrocytes are involved in maintaining the blood-brain barrier, clearing α-synuclein, metabolizing glutamate and fatty acids, and protecting neurons. The interactions among astrocytes, microglia, and oligodendrocytes exert dual effects on PD progression. Additionally, the recently recognized phenomena of ferroptosis and cuproptosis have been associated with astrocytic activity. The interplay and regulatory mechanisms linking these forms of cell death to apoptosis and pyroptosis of immune cells in the brain warrant further investigation. This review is intended for researchers, healthcare professionals, and clinicians involved in the study and treatment of PD and its related complications. To ensure comprehensive and unbiased coverage, a systematic literature search was conducted using major scientific databases such as PubMed, Scopus, and Web of Science. Keywords included "Parkinson's disease", "astrocyte", "brain", "signaling mechanisms", and "α-synuclein". Articles were selected based on their relevance to astrocyte-PD interactions, while studies lacking scientific rigor or relevance were excluded. In summary, this review synthesizes current understanding of astrocytic function and mechanisms in PD and proposes potential therapeutic directions based on these insights.