PMID- 19535823
OWN - NLM
STAT- MEDLINE
DCOM- 20091027
LR  - 20161021
IS  - 1732-2693 (Electronic)
IS  - 0032-5449 (Linking)
VI  - 63
DP  - 2009 Jun 15
TI  - [The genetics of dementias. Part 1: Molecular basis of frontotemporal dementia 
      and parkinsonism linked to chromosome 17 (FTDP-17)].
PG  - 278-86
AB  - Frontotemporal dementia (FTD), characterized by neurodegeneration mainly in the 
      frontal and temporal lobes, accounts for ca. 10-15% of all dementias. In 1892 the 
      Czech-German neuropsychiatrist Arnold Pick reported the fi rst case of FTD in a 
      71-year-old patient suffering from progressive dementia, memory disturbances, and 
      aphasia associated with frontal and temporal lobe atrophy and the presence of 
      neuronal inclusions. Later the inclusions were named Pick bodies.The 
      neuropathological hallmark of FTD is very differentiated. In contrast to 
      Alzheimer's disease(AD), there are neither senile plaques nor neurofibrillary 
      tangles in the brains of FTD patients.Frontotemporal dementias are tauopathies, a 
      group of disorders caused by aberrant metabolism of tau protein, a family of 
      proteins associated with microtubules (MAPT: macro-tubule-associated tau 
      protein). In the nervous system the protein stabilizes microtubules in neuronal 
      axons and is thus responsible for crucial processes in neuron metabolism, such as 
      signal transduction, plasticity,and intracellular transport. In the human brain, 
      six isoforms are produced from the MAPT gene (chromosome 17 q21.2) by alternative 
      mRNA splicing. The isoforms differ in the number of amino acids in the protein 
      chain, the presence of three (3R tau type) or four (4R tau type) domains 
      responsible for binding to microtubules, and one or two inserts containing from 
      29 to 58 amino acids. The isoforms are modified posttranslationally by 
      hyperphosphorylation, glycation,or oxidation, which can change the protein's 
      properties and disturb its normal function. Altered metabolism of tau protein 
      changes its interactions with tubulin, leading to destabilization of the 
      microtubule structure and initiating the generation of toxic tau aggregates. The 
      fi rst mutations in the MAPT gene responsible for frontotemporal dementia and 
      parkinsonism linked to chromosome 17 (FTDP-17) were found in 1998. So far over 40 
      mutations in the MAPT gene have been identified, mainly in families with 
      autosomal dominant FTDP-17 but also in sporadic families with Pick's disease and 
      AD. The known DNA changes have been classified according to their molecular 
      effects into at least two groups: mutations that change the biochemical 
      properties of tau protein and mutations that alter the alternative splicing of 
      mRNA and lead very often to the overproduction of the 4R tau isoform. The 
      imbalance in the ratio of the synthesized 3R and 4R tau isoforms stimulates 
      protein aggregation and initiates neurodegeneration, leading to the development 
      of dementia.
FAU - Kowalska, Anna
AU  - Kowalska A
AD  - Instytut Genetyki Czlowieka PAN w Poznaniu, 60-479 Poznan. 
      annkowal@rose.man.poznan.pl
LA  - pol
PT  - English Abstract
PT  - Journal Article
PT  - Review
TT  - Genetyka zespolow otepiennych. Czesc 1: Podloze molekularne otepienia 
      czolowo-skroniowego i parkinsonizmu sprzezonego z chromosomem 17 (FTDP-17).
DEP - 20090615
PL  - Poland
TA  - Postepy Hig Med Dosw (Online)
JT  - Postepy higieny i medycyny doswiadczalnej (Online)
JID - 101206517
RN  - 0 (MAPT protein, human)
RN  - 0 (Protein Isoforms)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Chromosomes, Human, Pair 17
MH  - Dementia/*genetics
MH  - Gene Expression Regulation
MH  - Humans
MH  - Parkinsonian Disorders/*genetics
MH  - Protein Isoforms/genetics
MH  - tau Proteins/*genetics/metabolism
RF  - 75
EDAT- 2009/06/19 09:00
MHDA- 2009/10/29 06:00
CRDT- 2009/06/19 09:00
PHST- 2009/06/19 09:00 [entrez]
PHST- 2009/06/19 09:00 [pubmed]
PHST- 2009/10/29 06:00 [medline]
AID - 888261 [pii]
PST - epublish
SO  - Postepy Hig Med Dosw (Online). 2009 Jun 15;63:278-86.