Scientists have discovered a key to unlocking the mystery of degenerative brain disorders such as Alzheimer's disease

Scientists have developed NeuM, a neuronal labeling technique that allows detailed monitoring of neuronal structure. Successful monitoring of neurological changes for up to 72 hours.

Alzheimer's disease Parkinson's disease, Parkinson's disease, and stroke are the main triad of neurodegenerative conditions. These disorders are characterized by the dysfunction and progressive deterioration of nerve cells, i.e. neurons. To understand the underlying mechanisms of these neurological conditions and formulate treatments, it is essential to have labeling techniques that enable visualization of neuronal changes under both healthy and pathological conditions.

A research team led by Dr. Kim Yeon-kyung from the Brain Science Institute at the Korea Institute of Science and Technology (Kist, in collaboration with the team of Professor Zhang Yong-tai from Pohang University of Science and Technology, announced the development of a next-generation neuronal labeling technology called NeuM. NeuM (selective neuronal membranes) selectively labels neuronal membranes, visualizing neuronal structures and allowing real-time monitoring of neuronal changes.

Researchers from Dr. Kim Yun-kyung's team at KIST are using the next generation neuronal labeling technology, NeuM, to visualize neurons in real-time and examine high-resolution images. Credit: Korea Institute of Science and Technology

Neurons continually modify their structure and function to transmit information from sensory organs to the brain, and organize thoughts, memories, and behaviors. Therefore, to overcome neurodegenerative diseases, it is necessary to develop techniques that selectively label living neurons for real-time monitoring. However, current gene- and antibody-based labeling techniques, which are commonly used to monitor neurons, suffer from decline Accuracy Long-term tracking is difficult due to its dependence on gene expression or specific proteins.

Advantages and capabilities of NeuM

NeuM, developed by the research team through molecular design of neurons, has excellent affinity for neuronal membranes, enabling long-term tracking and high-resolution imaging of neurons. Fluorescent sensors within NeuM attach to neuronal membranes using live cell activity, and emit fluorescent signals upon excitation by specific wavelengths of light. This visualization of neuronal cell membranes allows detailed observation of nerve terminal structures and high-resolution monitoring of neuronal differentiation and interactions.

Molecular design of selective labeling of neuronal membranes. Credit: Korea Institute of Science and Technology

NeuM, as the first technology to stain cell membranes through endocytosis in living neurons, shows selective reactivity toward living cells, excluding dead cells without internalization. Furthermore, the research team succeeded in extending the monitoring time of neurons from a mere 6 hours to 72 hours, allowing dynamic changes in living neurons to be captured over an extended period in response to environmental changes.

NeuM is expected to provide insights into research and treatment development for neurodegenerative diseases, for which there is currently no cure. These diseases, including Alzheimer's disease, result from damage to nerve cells due to the production of toxic proteins such as amyloid and the influx of inflammatory substances. Close monitoring of NeuM for neurological changes can effectively facilitate the evaluation of candidate therapeutic compounds.

“The NeuM, which has been developed this time, can distinguish between aging and degenerating neurons, becoming a crucial tool in elucidating the mechanisms of degenerative brain disorders and developing treatments,” Dr. Kim said. He also added: “In the future, we plan to improve NeuM for more precise analysis of neurons by designing fluorescent wavelengths to distinguish colors such as green and red.”

Reference: “NeuM: a neuron-selective probe incorporated into living neuronal membranes via clathrin-mediated enhanced endocytosis in primary neurons” by Yoonsik Song, Lizaveta Gotina, Kyu-Hyun Kim, Jung-Yul Lee, Solji Shin, Hira Aziz, Dong-Min Kang, Xiao December 7, 2023, December 7, 2023 Angewandte Chemie International Edition.
doi: 10.1002/anie.202312942

This research was supported by the Ministry of Science and ICT (Minister Lee Jung-ho) through KIST Major Projects and the Overcoming Dementia Project (RS-2023-00261784).