Optogenetics and Opsins: Illuminating New Avenues for Alzheimer's Disease Research

Optogenetics is a technique commonly used in our study of neural functional loops to precisely control the activity of specific neurons. It involves introducing exogenous light-sensitive proteins into neurons and irradiating them with specific wavelengths for the purpose of controlling ion channels.

Creative Biolabs brings you an introduction and a guide to optogenetics application and opsin selection in Alzheimer's disease research.

Overview of Optogenetic Technologies and Opsins

Optogenetics is an experimental technique that combines genetics and optics to enable scientists to control the timing and spatialization of specific events in living cells. The key components of this technique are photosensitive proteins, which can be activated or inhibited by light.

Opsins are a class of proteins that can sense light signals and translate them into biological effects. These proteins are widely found in nature in organisms such as cyanobacteria, green algae, and fungi. Several types of light-sensitive proteins have been discovered and utilized, including light-activated ion channels, light-inhibited ion channels, and light-activated enzymes.

Types of Light Sensitive Proteins

Light-sensitive proteins can be categorized into several main types, including light-activated ion channels, light-inhibited ion channels, and light-activated enzymes. The following is a brief overview of these types.

• Light-activated ion channels
  This type of light-sensitive protein opens upon exposure to light, allowing ions to pass through. A typical example is ChR2 (Channelrhodopsin-2), which is a light-activated cation channel that allows the passage of primarily sodium and potassium ions. ChR2 opens upon exposure to blue light, resulting in depolarization of the cell membrane, which activates neurons.
• Light-inhibited ion channels
  This class of light-sensitive proteins closes upon exposure to light, preventing the passage of ions. A typical example is NpHR (Halorhodopsin), which is a photoinhibitory chloride channel. npHR closes when exposed to yellow light, resulting in hyperpolarization of the cell membrane and thus inhibiting neuronal activity.
• Light-activated enzymes
  This class of light-sensitive proteins activates their enzymatic activity upon exposure to light, thereby affecting intracellular signaling. A typical example is OptoXR (light-activated G-protein-coupled receptor), which activates specific G-protein-coupled receptor pathways upon exposure to light, thereby modulating intracellular signaling.

Opsins in Alzheimer's Disease

Optogenetics shows great potential in Alzheimer's disease research. The following are the various types of light-sensitive proteins used in AD.

Fig. 1 Optogenetics illuminates memory circuits impaired in AD. (Mirzayi P, et al., 2022)

• Mapping and manipulation of neural circuits
  By using light-activated ion channels (e.g., ChR2) and light-inhibited ion channels (e.g., NpHR), specific neural circuits can be precisely manipulated to study their role in AD. For example, they can activate or inhibit specific neurons to see how this affects memory and learning.
• Research on disease models
  Optogenetics can also be used to create and study animal models of AD. By altering the genes of the animals, it is possible to mimic the symptoms of AD and then use light-sensitive proteins (such as ChR2 and NpHR) to study the causes of these symptoms.
• Development of new therapies
  Light-activated enzymes such as OptoXR can be used to study the role of intracellular signaling in AD, which could help develop new treatments. For example, by using photosensitizing proteins to manipulate neuronal activity, it may be possible to find ways to restore memory and learning ability.

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Reference

1. Mirzayi P, et al. Optogenetics: Implications for Alzheimer's disease research and therapy. Molecular brain, 2022, 15(1): 1-14.

For Research Use Only. Not For Clinical Use.