Revolutionizing Neuron Observation for Disease Insight

Summary: A new neuron labeling technology, NeuM, has been developed, offering unprecedented insights into the mechanisms of neurodegenerative disorders like Alzheimer’s and Parkinson’s disease. NeuM enables selective, high-resolution visualization of neuronal membranes, allowing for the detailed monitoring of neuronal changes in real-time.

This innovative technology overcomes the limitations of existing labeling methods by providing long-term tracking capabilities and high accuracy without reliance on gene expression or proteins. Expected to advance research and therapy development for neurological diseases, NeuM marks a significant leap forward in understanding and treating conditions previously deemed incurable.

Key Facts:

1. NeuM allows for the selective labeling and long-term tracking of neuronal membranes, facilitating the observation of dynamic neuronal changes.
2. The technology provides a powerful tool for researching neurodegenerative disorders, enabling the precise monitoring of neuron degeneration and the effects of therapeutic compounds.
3. Developed through molecular design, NeuM stands out by offering selective reactivity to living cells, significantly extending the observation window of neuronal activities to up to 72 hours.

Source: KIST

Alzheimer’s disease and Parkinson’s disease, along with stroke, are among the top three neurodegenerative disorders, characterized by the malfunction and progressive degeneration of neurons, the nerve cells.

Understanding the mechanisms underlying these neurological disorders and developing therapies requires labeling technologies that can visualize neuronal changes not only in normal conditions but also in disease states.

A research team led by Dr. Kim Yun Kyung from the Brain Science Institute at the Korea Institute of Science and Technology (KIST), in collaboration with Professor Chang Young-Tae’s team from Pohang University of Science and Technology, has announced the development of a next-generation neuron labeling technology called NeuM.

NeuM (Neuronal Membrane-selective) selectively labels neuronal membranes, visualizing neuronal structures and allowing real-time monitoring of neuronal changes.

Neurons continuously modify their structure and function to transmit information from sensory organs to the brain, regulating thoughts, memories, and behaviors. Therefore, to overcome degenerative neurological diseases, it is essential to develop techniques that selectively label living neurons for real-time monitoring.

However, current gene-based and antibody-based labeling technologies, commonly used to observe neurons, suffer from low accuracy and difficulty in long-term tracking due to their dependence on specific gene expression or proteins.

NeuM, developed by the research team through molecular design of neuronal cells, possesses excellent binding affinity to neuronal membranes, enabling long-term tracking and high-resolution imaging of neurons.

The fluorescent probes within NeuM bind to neuronal membranes utilizing the activity of living cells, emitting fluorescent signals upon excitation by specific wavelengths of light. This visualization of neuronal membranes allows for detailed observation of neuronal terminal structures and high-resolution monitoring of neuronal differentiation and interactions.

NeuM, as the first technology to stain cell membranes through endocytosis in living neurons, exhibits selective reactivity towards living cells, excluding dead cells without internalization.

Moreover, the research team has succeeded in extending the observation time of neurons from a mere 6 hours to up to 72 hours, enabling the capture of dynamic changes in living neurons over an extended period in response to environmental changes.

NeuM is expected to provide insights into research and therapy development for degenerative neurological diseases, for which there are currently no cures. These diseases, including Alzheimer’s, result from neuronal damage due to the production of toxic proteins such as amyloid and the influx of inflammatory substances.

NeuM’s precise observation of neuronal changes can effectively facilitate the evaluation of candidate therapeutic compounds.

Dr. Kim stated, “NeuM, developed this time, can distinguish aging and degenerating neurons, becoming a crucial tool in elucidating the mechanisms of degenerative brain disorders and developing treatments.”

He further added, “In the future, we plan to refine NeuM for even more precise analysis of neurons by designing fluorescence wavelengths to distinguish colors such as green and red.”

About this neurotech research news

Author: Kim Yun Kyung
Source: KIST
Contact: Kim Yun Kyung – KIST
Image: The image is credited to Neuroscience News

Original Research: Open access.
“NeuM: A Neuron-Selective Probe Incorporates into Live Neuronal Membranes via Enhanced Clathrin-Mediated Endocytosis in Primary Neruons” by Kim Yun Kyung et al. Angewandte Chemie

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Abstract

NeuM: A Neuron-Selective Probe Incorporates into Live Neuronal Membranes via Enhanced Clathrin-Mediated Endocytosis in Primary Neruons

The development of a small-molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions.

Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron-selectivity nor the cellular localization has been determined.

Here, we introduce NeuM, a derivative of NeuO, designed to target neuronal cell membranes. Furthermore, we elucidate the mechanism behind the selective neuronal membrane trafficking that distinguishes neurons.

In an aqueous buffer, NeuM autonomously assembles into micellar structures, leading to the quenching of its fluorescence (Φ=0.001).

Upon exposure to neurons, NeuM micelles were selectively internalized into neuronal endosomes via clathrin-mediated endocytosis.

Through the endocytic recycling pathway, NeuM micelles integrate into neuronal membrane, dispersing fluorescent NeuM molecules in the membrane (Φ=0.61).

Molecular dynamics simulations demonstrated that NeuM, in comparison to NeuO, possesses optimal lipophilicity and molecular length, facilitating its stable incorporation into phospholipid layers.

The stable integration of NeuM within neuronal membrane allows the prolonged monitoring of neurons, as well as the visualization of intricate neuronal structures.