May 18, 2024

New Molecular Mechanism Identified for Neuronal Death

A recent study published in the journal Science Signaling has discovered a molecular complex that affects the transport of mitochondria within neurons, which in turn regulates neuronal death. The complex, found exclusively in the most evolved mammals, has the potential to lead to new therapeutic targets for neurodegenerative diseases such as Parkinson’s, neuromuscular diseases, and certain types of tumors.

The study, conducted on animal models and cell cultures, was led by Professor Eduardo Soriano from the University of Barcelona and the Institute of Neurosciences of the UB (UBneuro), along with researcher Anna María Aragay from the Spanish National Research Council (CSIC) and the Institute of Molecular Biology of Barcelona (IBMB-CSIC). In neurons, the transport process of mitochondria is crucial for providing energy to neurotransmission and neuronal functions. This process relies on the precise distribution of mitochondria within neurons.

The study reveals the presence of the Alex3/Gαq mitochondrial complex, which interacts with the machinery responsible for distributing and transporting mitochondria along the axons and dendrites of neurons. This interaction is dependent on the Gq protein and the Alex3 mitochondrial protein. The researchers found that the Alex3/Gαq complex not only affects mitochondrial transport and function but also has an impact on neuronal physiology, movement control, and viability. Inactivating this system, as seen in mice with a deficiency of the Alex3 protein in the central nervous system, resulted in reduced mitochondrial trafficking, decreased dendritic and axonal arborizations, motor deficits, and even neuronal death.

Previous studies by the authors had already identified the Alex3 and Gαq proteins as regulators of mitochondrial transport but did not explain their interaction or the specific molecular mechanisms involved. According to this new study, the interaction of the Alex3/Gαq complex is regulated through G protein-coupled receptors (GPCR), which play a role in various functions of the organism, such as neurotransmission, hormone regulation, and cannabinoid signaling.

The activation of GPCRs not only affects mitochondrial distribution but also its function. One notable effect is the impact on neuronal growth and viability. The study suggests that molecules interacting with GPCRs could regulate several aspects of mitochondrial biology, indicating a potential avenue for therapeutic intervention in neurodegenerative diseases.

The discovery of this molecular mechanism provides valuable insights into the intricate processes that govern neuronal functions and survival. By understanding the mechanisms underlying neuronal death, researchers can develop targeted therapies that may ultimately help in the treatment of neurodegenerative diseases.

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1. Source: Coherent Market Insights, Public sources, Desk research
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