Outlining new strategies against neurodegenerative diseases

by time news

2023-10-06 20:45:56

Neurons are capable of forming vesicles that transport molecules—proteins, lipids, RNA, etc.—to the outside, and regulate communication between nerve cells. These are extracellular vesicles, and today there are still many unknowns about the role they play in communication between neurons in the nervous system.

A new study from the University of Barcelona (UB) could boost the design of future strategies to regenerate brain areas damaged in neurodegenerative diseases. The work emphasizes the role of extracellular vesicles derived from neurons in the processes that modulate synaptic plasticity and neuronal signaling pathways. Furthermore, the results outline a new scenario for using these extracellular vesicles derived from healthy neurons—capable of transporting molecules between cells—in treatments against neurodegenerative diseases.

The study has predoctoral student Julia Solana-Balaguer as its first author, and is directed by Professor Cristina Malagelada, from the Faculty of Medicine and Health Sciences and the Institute of Neurosciences (UBneuro) of the University of Barcelona. Other prominent researchers from the UBneuro, the Faculty of Physics and the Institute of Complex Systems (UBICS) of the UB, the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and the areas of the Networked Biomedical Research Center for Neurodegenerative Diseases also participate. (CIBERNED) and Epidemiology and Public Health (CIBERESP), in Spain, among other entities.

The new study, carried out with in vitro neuronal cultures from animal models, reveals that the aforementioned vesicles are capable of transporting proteins—for example, PSD-95 and VGLUT-1—and other determining factors in the communication processes between neurons.

«Although extracellular vesicles have been proposed as regulators of intercellular communication in the brain, most studies demonstrate this in models that are far from a physiological state and in vesicles whose origin is unknown. In this study we demonstrate that, in a physiological model without pathologies, the specific extracellular vesicles of neurons regulate neuron-to-neuron communication and promote synaptic plasticity,” details Cristina Malagelada, professor at the UB Department of Biomedicine and researcher at CIBERNED.

Members of the research team. From left to right: Melike Kucukerden, Jordi Alberch, Mercè Masana, Júlia Solana, Cristina Malagelada and Esther Pérez-Navarro. In the column (descending direction): Genís Campoy, Núria Martín-Flores, Letícia Pérez-Sisqués, Laia Sitjà, Ana Gámez-Valero, Eulàlia Martí and Jordi Soriano. (Photo: UB)

New strategies to combat neurodegeneration

Within the framework of the study, the team has applied complementary techniques to isolate the extracellular vesicles released by neurons, such as sequential ultracentrifugation or size exclusion chromatography. In addition, techniques have been used to characterize them, such as nanoparticle tracking analysis and transmission electron microscopy. These vesicles have also been used to perform treatments on healthy neurons and neurons deprived of nutrients.

«Once neuron-neuron communication is understood in a non-pathological state, we want to address this question in a context of neurodegeneration. Therefore, it is crucial to be able to characterize the vesicles released by neurons in neurodegenerative diseases in order to understand the progression of these pathologies. Furthermore, we want to explore whether in a pathological model we can reverse some more neurodegenerative trait with the treatment of extracellular vesicles derived from healthy neurons,” closes the researcher.

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The study is titled “Neuron-derived extracellular vesicles contain synaptic proteins, promote spine formation, activate TrkB-mediated signaling, and preserve neuronal complexity.” And it has been published in the academic journal Journal of Extracellular Vesicles. (Source: UB)

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