J Yeungnam Med Sci.  2022 Oct;39(4):269-277. 10.12701/jyms.2021.01683.

Optogenetic neuromodulation with gamma oscillation as a new strategy for Alzheimer disease: a narrative review

• Ko H
• Yoon SP

• KMID: 2534653
• DOI: http://doi.org/10.12701/jyms.2021.01683

Abstract

The amyloid hypothesis has been considered a major explanation of the pathogenesis of Alzheimer disease. However, failure of phase III clinical trials with anti-amyloid-beta monoclonal antibodies reveals the need for other therapeutic approaches to treat Alzheimer disease. Compared to its relatively short history, optogenetics has developed considerably. The expression of microbial opsins in cells using genetic engineering allows specific control of cell signals or molecules. The application of optogenetics to Alzheimer disease research or clinical approaches is increasing. When applied with gamma entrainment, optogenetic neuromodulation can improve Alzheimer disease symptoms. Although safety problems exist with optogenetics such as the use of viral vectors, this technique has great potential for use in Alzheimer disease. In this paper, we review the historical applications of optogenetic neuromodulation with gamma entrainment to investigate the mechanisms involved in Alzheimer disease and potential therapeutic strategies.

Keyword

Alzheimer disease; Amyloid beta; Gamma oscillation; Optogenetics

Figure

• 

  Fig. 1. Schematic overview of optogenetics. (A) Genetic materials containing microbial opsin are introduced in viral vectors such as adeno-associated virus to transduce microbial opsins in laboratory mice. The vector is injected to target neuron cells and express opsins. (B) Creating transgenic mice through Cre recombinase is a novel approach to develop opsin-expressing mice. Through Cre-mediated recombination of loxP sites, microbial opsins can be expressed in specific cells that express Cre recombinase. (C) After expression of microbial opsins, light sources introduce light to specific sites in the laboratory animals. Some microbial opsins such as channelrhodopsin activate signals and others such as halorhodopsin inhibit signals. P, promoter; LED, light-emitting diode; OLED, organic LED.

• 

  Fig. 2. Timeline of optogenetics and gamma entrainment related to the development of therapeutic strategies for Alzheimer disease (AD). Aβ, amyloid-beta; white arrowhead, related to gamma entrainment; black arrowhead, related to optogenetics.

Reference

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