Abstract
Cell cycle reentry is a unified mechanism shared by several neurodegenerative diseases, including Alzheimer’s disease (AD) and Ataxia Telangiectasia (A-T). This phenotype is often related to neuroinflammation in the central nervous system. To mimic brain inflammation in vitro, we adopted the previously established method of using conditioned medium collected from activated THP-1 cells and applied it to both differentiated HT22 cells and primary neurons. Unscheduled cell cycle events were observed in both systems, indicating the potential of this approach as an in vitro model of neurodegenerative disease. We used this assay to measure the neuroprotective effects of New Zealand green-lipped mussel extract, PCSO-524®, to protect post-mitotic cells from cell cycle reentry. We found that, both in vitro and in an animal model, PCSO-524® displayed promising neuroprotective effects, and thus has potential to postpone or prevent the onset of neurodegenerative disease.
Highlights
The neurons of the mammalian central nervous system (CNS) are fully differentiated cells that are permanently post-mitotic in the adult
As an initial screen for the effects of the drug on neuronal cell cycle events, we used HT22 cells, a neuroblastoma line that expresses neuron-like characteristics after differentiation [33]
HT22 cells were seeded in 24-well plates and induced to differentiate by adding 1 mM dibutyryl cyclic AMP
Summary
The neurons of the mammalian central nervous system (CNS) are fully differentiated cells that are permanently post-mitotic in the adult. It has been reported that the conditioned medium from Aβ activated human monocyte THP-1 cells and primary microglia could induce neuronal cell cycle and cell death [22]. This observation was later confirmed by other studies that this neuronal cell cycle-related cell death resulted from the pro-inflammatory cytokines TNFα [16] and glutamate [24]. Based on these studies, we have adopted an in vitro model of unscheduled cell cycle events triggered by neuroinflammation as a screening technique [22] and used it to screen novel sources of natural products for neuroprotective agents. We extended our findings to an animal model of neurodegeneration, where PCSO-524® proved effective, implying its potential to delay or prevent the onset of neurodegenerative disease
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