Akademik Veri Yönetim Sistemi
ACS omega, cilt.8, sa.48, ss.45519-45534, 2023 (SCI-Expanded, Scopus)
Neurodegeneration is a condition in which the neuronal structure and functions are altered with reduced neuronal survival and increased neuronal death in the central nervous system (CNS). Amyloid-beta (A beta) is the pathological hallmark of a common neurodegenerative disorder, Alzheimer disease. Parkinson disease and dementia with Lewy bodies are among alpha-synucleinopathies characterized by abnormal accumulation of insoluble alpha-synuclein protein. Neuroinflammation is seen in those neurodegenerative disorders regulated by cytokines and chemokines released from neurons, microglia, and astrocytes. Our study aimed to (1) define steady-state levels of cytokines and immune response modulators in SH-SY5Y cells that were differentiated into neuron-like cells and (2) compare the levels of target cytokines in cellular models of neurodegenerative disorders, namely, AD, PD, and DLB-like pathologies. AD, PD, and DLB-like pathologies were established by 6 mu M A beta 1-42 administration, SNCA (alpha-synuclein) overexpression, and SNCA overexpression was followed by A beta 1-42 treatment, respectively. Alterations in the levels of 40 released inflammatory proteins (IPs) were analyzed by chemiluminescence-based Western/dot blot. Overexpression of human alpha-synuclein and administration of A beta 1-42 significantly changed the profile of IPs secretion, with particularly significant changes in CSF2, CCL5, CXCL8, CXCL10, ICAM1, IL1B, and IL16. Bioinformatics analysis revealed possible interactions between alpha-synuclein and IL1B. While TGF1, CCL2, TNF, IL10, IL4, and IL1B IPs were associated with A beta 1-42, A beta 1-42 treatment together with alpha-synuclein, overexpression is associated only with the IL6 protein. Consequently, AD, PD, and DLB-like pathologies might exert significant but different alterations in the inflammatory response.