HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The novel Tau mutation G335S: clinical, neuropathological and molecular characterization.

Abstract
Mutations in Tau cause the inherited neurodegenerative disease, frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known coding region mutations cluster in the microtubule-binding region, where they alter the ability of tau to promote microtubule assembly. Depending on the tau isoforms, this region consists of three or four imperfect repeats of 31 or 32 amino acids, each of which contains a characteristic and invariant PGGG motif. Here, we report the novel G335S mutation, which changes the PGGG motif of the third tau repeat to PGGS, in an individual who developed social withdrawal, emotional bluntness and stereotypic behavior at age 22, followed by disinhibition, hyperorality and ideomotor apraxia. Abundant tau-positive inclusions were present in neurons and glia in the frontotemporal cortex, hippocampus and brainstem. Sarkosyl-insoluble tau showed paired helical and straight filaments, as well as more irregular rope-like filaments. The pattern of pathological tau bands was like that of Alzheimer disease. Experimentally, the G335S mutation resulted in a greatly reduced ability of tau to promote microtubule assembly, while having no significant effect on heparin-induced assembly of recombinant tau into filaments.
AuthorsSalvatore Spina, Jill R Murrell, Hirotaka Yoshida, Bernardino Ghetti, Niamh Bermingham, Brian Sweeney, Stephen R Dlouhy, R Anthony Crowther, Michel Goedert, Catherine Keohane
JournalActa neuropathologica (Acta Neuropathol) Vol. 113 Issue 4 Pg. 461-70 (Apr 2007) ISSN: 0001-6322 [Print] Germany
PMID17186252 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • tau Proteins
  • Serine
  • Glycine
Topics
  • Adult
  • DNA Mutational Analysis (methods)
  • Dementia (genetics, metabolism, pathology)
  • Glycine (genetics)
  • Humans
  • Male
  • Microscopy, Electron, Transmission
  • Microtubules (pathology, ultrastructure)
  • Mutation
  • Neurofibrillary Tangles (metabolism, pathology, ultrastructure)
  • Serine (genetics)
  • tau Proteins (genetics, ultrastructure)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: