The Effects of Mesenchymal Stem Cell on Calpains, Glycogen Synthase Kinase-3β, and Ryanodine Receptor 3 in Animal Models of Alzheimer’s Disease: A Systematic Review
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Abstract
Alzheimer’s disease (AD) is a major common neurodegenerative disease characterized by progressive memory loss and decline in cognitive function, leading to dementia. Unlike pharmacological therapies, which are targeted toward symptoms, cell-based therapies target the underlying causes of AD. Therapies using mesenchymal stem cells (MSC) that target several important proteins such as calpains, glycogen synthase kinase 3-beta (GSK3β), and ryanodine receptor 3 (RYR3) related to amyloid-beta (Aβ) which contribute to AD pathophysiology need further investigation. This systematic review explored studies that examined the effects of MSC on the expression of calpains, GSK3β, and RYR3 in mouse models of AD. A literature search of Medline/PubMed electronic database identified seven studies that met the inclusion criteria. These studies suggested that MSC may be associated with reduced GSK3β activity in AD mice by activating its inhibitory pathway and suppressing its activation pathway. MSC could also suppress RYR3 expression in AD mice, reducing calcium (Ca2+) levels in the cytosol. The beneficial effects of reduced GSK3β and RYR3 activity after MSC treatment include improved cognitive function, and reduced tau phosphorylation and Aβ plaques in AD mice. This systematic review emphasizes the need for further research on which MSC types, doses, and administration routes are most effective, as well as the immune response and effects in humans.
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