Tunneling Nanotube: An Enticing Cell–Cell Communication in the Nervous System

SIMPLE SUMMARY: This review highlights the role of tunneling nanotubes (TNTs) and TNT-like structures in the nervous system. TNTs are thin, hollow plasma membrane projections that directly connect the lumen of one cell to the lumen of another cell, thereby transferring different cargoes between the two connected cells. TNTs have been shown to play very prominent roles in neuronal development and serve as highways for neurodegenerative diseases in the brain. Here, we discuss different crucial aspects of TNTs like their architecture, TNTs’ involvement in different pathological and physiological conditions in the nervous system, and the mechanisms involved in their formation. In this review, we also discuss different challenges involved in TNT research and its future prospects. ABSTRACT: The field of neuroscience is rapidly progressing, continuously uncovering new insights and discoveries. Among the areas that have shown immense potential in research, tunneling nanotubes (TNTs) have emerged as a promising subject of study. These minute structures act as conduits for the transfer of cellular materials between cells, representing a mechanism of communication that holds great significance. In particular, the interplay facilitated by TNTs among various cell types within the brain, including neurons, astrocytes, oligodendrocytes, glial cells, and microglia, can be essential for the normal development and optimal functioning of this complex organ. The involvement of TNTs in neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, has attracted significant attention. These disorders are characterized by the progressive degeneration of neurons and the subsequent decline in brain function. Studies have predicted that TNTs likely play critical roles in the propagation and spread of pathological factors, contributing to the advancement of these diseases. Thus, there is a growing interest in understanding the precise functions and mechanisms of TNTs within the nervous system. This review article, based on our recent work on Rhes-mediated TNTs, aims to explore the functions of TNTs within the brain and investigate their implications for neurodegenerative diseases. Using the knowledge gained from studying TNTs could offer novel opportunities for designing targeted treatments that can stop the progression of neurodegenerative disorders.