Electromagnetic field induced activation of amyloid-β degrading enzyme,neprilysin,for accelerated Alzheimer's disease therapy

Abstract

Background

Amyloid-β accumulation and misfolding are key features of Alzheimer's disease (AD), contributing to synaptic dysfunction, neuroinflammation, and neuronal loss. Normally, amyloid-β is cleared by chaperone-assisted folding, enzymes such as neprilysin and insulin-degrading enzyme, and autophagy pathways. In AD, these mechanisms become impaired, leading to toxic aggregation. Enhancing the activity of endogenous degrading enzymes offers a promising therapeutic approach, with electromagnetic (EM) fields emerging as a potential noninvasive method to promote amyloid-β clearance.

Objective

This study computationally evaluates whether controlled EM wave exposure (100–900 MHz) delivered through a waveguide can enhance amyloid-β degradation by accelerating enzyme activation and reducing Gibbs free energy barriers.

Methods

A mechanistic model linking EM stimulation with cellular stress responses, chaperone activity, enzyme delivery, and autophagy was developed. Quantum-chemical simulations evaluated changes in Gibbs free energy and reaction rates under no EM field, low-intensity EM (1.0 × 10⁻¹¹ a.u.), and optimized EM intensity (5.09 × 10⁻¹⁰ a.u.).

Results

Computational simulations revealed that EM stimulation enhances enzymatic activation by lowering the Gibbs free energy barrier. Without an electric field, ΔG was 66.00 kJ·mol⁻¹ with a reaction rate of 56.5 s⁻¹. Low-intensity EM slightly reduced ΔG to 65.87 kJ·mol⁻¹ and increased the rate to 67.5 s⁻¹. At optimized EM intensity, ΔG decreased to 52.10 kJ·mol⁻¹, raising the reaction rate to 1.18 × 10⁴ s⁻¹, indicating significantly accelerated enzyme activity and improved amyloid-β degradation potential.

Conclusions

The integrated model shows that optimized EM stimulation enhances enzyme-mediated amyloid-β degradation by lowering energy barriers and increasing reaction rates, supporting a potential noninvasive therapeutic strategy for AD.