The Role of Mesenchymal Stem Cells in Regulating Astrocytes-Related Synapse Dysfunction in Early Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD), a neurodegenerative disease, is characterized by the presence of extracellular amyloid-β (Aβ) aggregates and intracellular neurofibrillary tangles formed by hyperphosphorylated tau as pathological features and the cognitive decline as main clinical features. An important cellular correlation of cognitive decline in AD is synapse loss. Soluble Aβ oligomer has been proposed to be a crucial early event leading to synapse dysfunction in AD. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function have been suggested in the pathogenesis of AD. Astrocytes may contribute to synapse dysfunction at an early stage of AD by participating in Aβ metabolism, brain inflammatory response, and synaptic regulation. While mesenchymal stem cells can inhibit astrogliosis, and promote non-reactive astrocytes. They can also induce direct regeneration of neurons and synapses. This review describes the role of mesenchymal stem cells and underlying mechanisms in regulating astrocytes-related Aβ metabolism, neuroinflammation, and synapse dysfunction in early AD, exploring the open questions in this field.

Therapeutic potential of mesenchymal stem cells for cerebral small vessel disease

“…Besides targeting the classical hallmarks of AD, MSCs can also target astrocytes to alleviate Aβ degradation, neuroinflammation, and synapse dysfunction in AD [ 121 ]. Moreover, MSC-transplanted rats have several astrocytes [ 122 ].…”

Use of Brain-Derived Stem/Progenitor Cells and Derived Extracellular Vesicles to Repair Damaged Neural Tissues: Lessons Learned from Connective Tissue Repair Regarding Variables Limiting Progress and Approaches to Overcome Limitations

“…Another parallel between MSC and NSC is their relative effectiveness in addressing tissue repair is that NSC/NPC and MSC may be more effective in acute situations in both the brain [ 41 , 42 , 43 , 44 , 45 , 46 ] and in connective tissues such as articular cartilage [ 47 , 48 ] than in chronic disease situations involving either the brain or connective tissues [ 23 , 49 , 50 , 51 ]. The latter may relate to the in vivo environments being very different, including the involvement of a disease process involving chronic inflammation and tissue degradation fragments, and thus neither cell source may function properly in the face of a chronic inflammatory process.…”

Mesenchymal Stem Cells Applications in Alzheimer's Disease

“…10 When treating AD with MSCs, MSCs proliferate astrocytes, metabolize glutamate and gamma-aminobutyrate, inhibit neural cell necrosis, and unleash growth factors (like brain-derived neurotrophic factor [BDNF]) to enhance neurogenesis by stimulating neural progenitor cells because of their antioxidant properties and antiapoptotic effects. 11,12 To stop additional tissue damage brought on by chronic neuroinflammation, MSCs also have modulatory effects on the immune system by bypassing or suppressing proinflammatory microglia (M1) activation and encouraging the activation of anti-inflammatory microglia (M2). Research has proven that MSCs can boost autophagy activation, which is likely to be the reason for the lysosomal clearance of Aβ plaques.…”