What causes synaptotoxicity in neurons?
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Synaptotoxicity in neurons is caused by various factors, including proteasome impairment, manganese (Mn) overexposure, amyloid-β (Aβ) oligomers, prion protein (PrPSc), and astrocyte-mediated interactions. Proteasome impairment leads to the accumulation of cleaved tau at the post-synaptic density (PSD), resulting in synaptic alterations and neuronal dysfunction . Mn overexposure induces α-synuclein (α-Syn) overexpression, which disrupts synaptic vesicle (SV) functions and impairs memory and synaptic plasticity . Aβ oligomers induce actin stabilization and cofilin phosphorylation, leading to synaptic impairment and synaptic loss . PrPSc exposure causes rapid retraction of dendritic spines, dependent on the expression of cellular prion protein (PrPC) and a polybasic region in PrPC . Astrocytes exacerbate tau mislocalization and synaptotoxicity through the interaction of astrocytic CXCL1 and neuronal CXCR2 receptors, highlighting them as a target for therapeutic intervention in Alzheimer's disease .
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| Papers (5) | Insight |
|---|---|
| The paper states that secretions from astrocytes stimulated with Aβ induce synaptotoxicity in neurons. | |
43 Citations | The paper states that exposure of cultured hippocampal neurons to PrPSc, the infectious isoform of the prion protein, causes rapid retraction of dendritic spines, leading to synaptotoxicity. |
| The provided paper states that manganese-induced α-synuclein overexpression leads to the dysregulation of Rab26-dependent autophagy, which promotes the accumulation of dysfunctional synaptic vesicles and ultimately causes synaptotoxicity in neurons. | |
| The paper does not explicitly state the cause of synaptotoxicity in neurons. | |
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