Enhancement of Cytoskeletal Tension Promotes Amyloid-β Aggregation on the Neuronal Cell Surface

TL;DR

This study shows that increasing cytoskeletal tension in neurons leads to more amyloid-beta aggregation, a key feature of Alzheimer's disease.

Contribution

The novel finding is that cytoskeletal tension directly promotes amyloid-beta aggregation on neuronal surfaces.

Findings

Jasplakinolide and calyculin A increased cytoskeletal tension and Aβ deposition on cell surfaces.

Quantum-dot-labeled Aβ nanoprobes revealed real-time Aβ aggregation on living cells.

Cytoskeletal tension was found to overcome membrane barriers for Aβ accumulation.

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that accounts for the majority of dementia cases. The accumulation of amyloid-β (Aβ) aggregates on neuronal surfaces is a known important event that typifies AD. Although cell membrane architecture and cytoskeletal tension are thought to be involved in the process of Aβ aggregation, it remains unclear how cytoskeleton-derived tension alters the function of cell membranes, which serve as a scaffold for Aβ aggregation. In this study, we investigated whether cytoskeletal tension promotes Aβ aggregation on neuroblastoma, SH-SY5Y cells. Cytoskeletal tension was enhanced by jasplakinolide, an actin depolymerization inhibitor, and calyculin A, a serine/threonine phosphatase inhibitor that promotes myosin II activation. Real-time imaging with quantum-dot-labeled Aβ nanoprobes revealed that both pharmacological treatments significantly increased Aβ deposition on the surface of living cells. Our findings suggest that cytoskeletal tension promotes Aβ aggregation over the membrane barrier, providing new insights into the biophysical mechanisms underlying Aβ accumulation in AD pathogenesis.

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