Tunneling nanotubes: The transport highway for astrocyte-neuron communication in the central nervous system

Tunneling nanotubes (TNTs) have emerged as pivotal structures for intercellular communication, enabling the transfer of cellular components across distant cells. Their involvement in neurological disorders has attracted considerable scientific interest. This review delineates the functions of TNTs within the central nervous system, examining their role in the transmission of bioenergetic substrates, and signaling molecules, and their multifaceted impact on both physiological and pathological processes, with an emphasis on neurodegenerative diseases. The review highlights the selectivity and specificity of TNTs as dedicated pathways for intercellular cargo delivery, particularly under stress conditions that provoke increased TNT formation. The potential of TNTs as therapeutic targets is explored in depth. We pay particular attention to the interactions between astrocytes and neurons mediated by TNTs, which are fundamental to brain architecture and function. Dysfunctions in these interactions are implicated in the spread of protein aggregates and mitochondrial anomalies, contributing to the pathogenesis of neurodegenerative diseases. The review culminates with a synthesis of the current understanding of TNT biology and identifies research gaps, advocating for intensified exploration into TNTs as a promising therapeutic frontier.