Novel Therapeutic Target Identified for Huntington’s Disease via Tunneling Nanotubes
Researchers from Florida Atlantic University have identified a promising new therapeutic target for Huntington’s disease by uncovering the molecular mechanism behind the spread of mutant huntingtin protein (mHTT) between neurons. The study reveals that mHTT travels through tunneling nanotubes (TNTs), tiny cellular bridges regulated by the protein Rhes. Using liquid chromatography–tandem mass spectrometry, the team discovered that Rhes interacts with Slc4a7, an intracellular pH sensor, to facilitate TNT formation and mHTT transmission. Inhibition of Slc4a7 significantly reduced TNT formation and suppressed the intercellular transfer of the toxic protein in cell cultures. Furthermore, in vivo experiments with Slc4a7 knock-out mice demonstrated a marked reduction in mHTT spread within the striatum, the brain region most affected by the disease. These findings fundamentally shift the understanding of Huntington’s progression, suggesting that blocking these microscopic tunnels could slow or halt disease advancement. This discovery opens new avenues for developing treatments not only for Huntington’s but potentially for other neurological disorders and cancers involving similar protein propagation mechanisms.
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Novel Therapeutic Target Identified for Huntington’s Disease via Tunneling Nanotubes
Researchers from Florida Atlantic University have identified a promising new therapeutic target for Huntington’s disease by uncovering the molecular mechanism behind the spread of mutant huntingtin protein (mHTT) between neurons. The study reveals that mHTT travels through tunneling nanotubes (TNTs), tiny cellular bridges regulated by the protein Rhes. Using liquid chromatography–tandem mass spectrometry, the team discovered that Rhes interacts with Slc4a7, an intracellular pH sensor, to facilitate TNT formation and mHTT transmission. Inhibition of Slc4a7 significantly reduced TNT formation and suppressed the intercellular transfer of the toxic protein in cell cultures. Furthermore, in vivo experiments with Slc4a7 knock-out mice demonstrated a marked reduction in mHTT spread within the striatum, the brain region most affected by the disease. These findings fundamentally shift the understanding of Huntington’s progression, suggesting that blocking these microscopic tunnels could slow or halt disease advancement. This discovery opens new avenues for developing treatments not only for Huntington’s but potentially for other neurological disorders and cancers involving similar protein propagation mechanisms.
BioTechniques