This review examines tunneling nanotubes (TNTs) — thin, actin-based membranous conduits — as a distinct mode of intercellular communication in the central nervous system, covering their physiological roles, pathological contributions, and implications for neural connectivity.
The authors argue that TNTs constitute a 'fourth pillar' of brain connectivity (alongside synapses, gap junctions, and extracellular signaling), with emerging evidence linking them to neurodegeneration, neuroinflammation, and neural repair — though most supporting data remain preclinical or in vitro.
The review is largely conceptual and synthesis-based; most cited TNT evidence derives from in vitro models, and direct in vivo demonstration of TNT function in the intact brain remains limited. No original experimental data are presented.
TNTs are not yet a clinical target, but clinicians managing neurodegenerative or neuroinflammatory diseases should be aware that intercellular spread of pathological cargo (e.g., misfolded proteins) may occur through TNT-mediated routes, a mechanism distinct from synaptic transmission.
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