PMID- 15615642
OWN - NLM
STAT- MEDLINE
DCOM- 20050203
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1739
IP  - 2-3
DP  - 2005 Jan 3
TI  - Mutations causing neurodegenerative tauopathies.
PG  - 240-50
AB  - Tau is the major component of the intracellular filamentous deposits that define 
      a number of neurodegenerative diseases. They include the largely sporadic 
      Alzheimer's disease (AD), progressive supranuclear palsy, corticobasal 
      degeneration, Pick's disease and argyrophilic grain disease, as well as the 
      inherited frontotemporal dementia and parkinsonism linked to chromosome 17 
      (FTDP-17). For a long time, it was unclear whether the dysfunction of tau protein 
      follows disease or whether disease follows tau dysfunction. This was resolved 
      when mutations in Tau were found to cause FTDP-17. Currently, 32 different 
      mutations have been identified in over 100 families. About half of the known 
      mutations have their primary effect at the protein level. They reduce the ability 
      of tau protein to interact with microtubules and increase its propensity to 
      assemble into abnormal filaments. The other mutations have their primary effect 
      at the RNA level and perturb the normal ratio of three-repeat to four-repeat tau 
      isoforms. Where studied, this resulted in a relative overproduction of tau 
      protein with four microtubule-binding domains in the brain. Individual Tau 
      mutations give rise to diseases that resemble progressive supranuclear palsy, 
      corticobasal degeneration or Pick's disease. Moreover, the H1 haplotype of Tau 
      has been identified as a significant risk factor for progressive supranuclear 
      palsy and corticobasal degeneration. At a practical level, the new work is 
      leading to the production of experimental animal models that reproduce the 
      essential molecular and cellular features of the human tauopathies, including the 
      formation of abundant filaments made of hyperphosphorylated tau protein and nerve 
      cell degeneration.
FAU - Goedert, Michel
AU  - Goedert M
AD  - MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. 
      mg@mrc-lmb.ac.uk
FAU - Jakes, Ross
AU  - Jakes R
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (MAPT protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Alzheimer Disease/*genetics
MH  - Animals
MH  - Brain/metabolism/pathology
MH  - Disease Models, Animal
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Microtubule-Associated Proteins/genetics
MH  - *Mutation
MH  - Nerve Degeneration
MH  - Neurodegenerative Diseases/genetics
MH  - Tauopathies/*genetics
MH  - tau Proteins/*genetics
RF  - 139
EDAT- 2004/12/24 09:00
MHDA- 2005/02/04 09:00
CRDT- 2004/12/24 09:00
PHST- 2004/08/17 00:00 [received]
PHST- 2004/08/17 00:00 [accepted]
PHST- 2004/12/24 09:00 [pubmed]
PHST- 2005/02/04 09:00 [medline]
PHST- 2004/12/24 09:00 [entrez]
AID - S0925-4439(04)00150-4 [pii]
AID - 10.1016/j.bbadis.2004.08.007 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2005 Jan 3;1739(2-3):240-50. doi: 
      10.1016/j.bbadis.2004.08.007.