Improvement of a therapeutic strategy for neuronal survival
2018
Karolinska Institutet, Stockholm, Sweden
Alzheimer's disease pathology involves early degeneration of cholinergic neurons and decreased levels of the nerve growth factor (NGF). Encapsulated cell technology to deliver NGF to the affected area and promote neuronal survival has already been tested in clinical trials. However, the results showed variability of encapsulated cells survival and NGF release. Here, an NGF overproducing human immortalized retinal epithelial cell line is treated with amyloid-beta peptides, interleukin 1 beta and the cerebrospinal fluid of patients with Alzheimer's disease, Lewy body dementia or subjective cognitive impairment to decipher the cause of low cell viability during the human trials. Only interleukin 1 beta had an impact on nerve growth factor production and the cerebrospinal fluid of Alzheimer's patients was more detrimental to NGF production than others. Three proteins involved in inflammation were differentially expressed in Alzheimer's patients cerebrospinal fluid, suggesting that it is responsible for the variability in survival of encapsulated cells. This human model allowed the researchers to identify key mechanisms influencing the success of their therapeutic strategies that can be further studied to improve the outcome of their treatment.
Cerebrospinal fluid from Alzheimer patients affects cell-mediated nerve growth factor production and cell survival in vitro
Homira Behbahani
Added on: 08-16-2021
[1] https://www.sciencedirect.com/science/article/abs/pii/S001448271830658X?[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
