Tunneling nanotubes: A novel pharmacological target for neurodegenerative diseases?

Pharmacol Res. 2021 Aug:170:105541. doi: 10.1016/j.phrs.2021.105541. Epub 2021 Mar 10.

Abstract

Diversiform ways of intercellular communication are vital links in maintaining homeostasis and disseminating physiological states. Among intercellular bridges, tunneling nanotubes (TNTs) discovered in 2004 were recognized as potential pharmacology targets related to the pathogenesis of common or infrequent neurodegenerative disorders. The neurotoxic aggregates in neurodegenerative diseases including scrapie prion protein (PrPSc), mutant tau protein, amyloid-beta (Aβ) protein, alpha-synuclein (α-syn) as well as mutant Huntington (mHTT) protein could promote TNT formation via certain physiological mechanisms, in turn, mediating the intercellular transmission of neurotoxicity. In this review, we described in detail the skeleton, the formation, the physicochemical properties, and the functions of TNTs, while paying particular attention to the key role of TNTs in the transport of pathological proteins during neurodegeneration.

Keywords: Intercellular communication; Neurodegenerative Diseases; Neurotoxic protein aggregates; Tunneling nanotubes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Communication*
  • Cell Membrane Structures / drug effects
  • Cell Membrane Structures / metabolism*
  • Cell Membrane Structures / pathology
  • Humans
  • Nanotubes
  • Nerve Degeneration*
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neuroprotective Agents / therapeutic use
  • Protein Aggregates
  • Protein Aggregation, Pathological
  • Protein Transport

Substances

  • Neuroprotective Agents
  • Protein Aggregates
  • Tunneling Nanotubes