PMID- 11749044
OWN - NLM
STAT- MEDLINE
DCOM- 20020221
LR  - 20061115
IS  - 1044-7431 (Print)
IS  - 1044-7431 (Linking)
VI  - 18
IP  - 6
DP  - 2001 Dec
TI  - FTDP-17 mutations in tau transgenic mice provoke lysosomal abnormalities and Tau 
      filaments in forebrain.
PG  - 702-14
AB  - The tauopathies, which include Alzheimer's disease (AD) and frontotemporal 
      dementias, are a group of neurodegenerative disorders characterized by 
      filamentous Tau aggregates. That Tau dysfunction can cause neurodegeneration is 
      indicated by pathogenic tau mutations in frontotemporal dementia and parkinsonism 
      linked to chromosome 17 (FTDP-17). To investigate how Tau alterations provoke 
      neurodegeneration we generated transgenic mice expressing human Tau with four 
      tubulin-binding repeats (increased by FTDP-17 splice donor mutations) and three 
      FTDP-17 missense mutations: G272V, P301L, and R406W. Ultrastructural analysis of 
      mutant Tau-positive neurons revealed a pretangle appearance, with filaments of 
      Tau and increased numbers of lysosomes displaying aberrant morphology similar to 
      those found in AD. Lysosomal alterations were confirmed by activity analysis of 
      the marker acid phosphatase, which was increased in both transgenic mice and 
      transfected neuroblastoma cells. Our results show that Tau modifications can 
      provoke lysosomal aberrations and suggest that this may be a cause of 
      neurodegeneration in tauopathies.
FAU - Lim, F
AU  - Lim F
AD  - Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma de Madrid, 28049 
      Madrid, Spain.
FAU - Hernandez, F
AU  - Hernandez F
FAU - Lucas, J J
AU  - Lucas JJ
FAU - Gomez-Ramos, P
AU  - Gomez-Ramos P
FAU - Moran, M A
AU  - Moran MA
FAU - Avila, J
AU  - Avila J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (tau Proteins)
RN  - EC 3.1.3.2 (Acid Phosphatase)
SB  - IM
MH  - Acid Phosphatase/metabolism
MH  - Animals
MH  - Cerebral Cortex/abnormalities/pathology/ultrastructure
MH  - Cytoskeleton/*metabolism/pathology/ultrastructure
MH  - Female
MH  - Hippocampus/abnormalities/pathology/ultrastructure
MH  - Humans
MH  - Immunohistochemistry
MH  - Lysosomes/*metabolism/pathology/ultrastructure
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Electron
MH  - Mutation/*genetics
MH  - Neuroblastoma
MH  - Neurodegenerative Diseases/*genetics/metabolism/pathology
MH  - Neurons/*metabolism/pathology/ultrastructure
MH  - Phosphorylation
MH  - Prosencephalon/*abnormalities/pathology/ultrastructure
MH  - Tumor Cells, Cultured
MH  - tau Proteins/*genetics/metabolism/ultrastructure
EDAT- 2001/12/26 10:00
MHDA- 2002/02/22 10:01
CRDT- 2001/12/26 10:00
PHST- 2001/12/26 10:00 [pubmed]
PHST- 2002/02/22 10:01 [medline]
PHST- 2001/12/26 10:00 [entrez]
AID - S1044-7431(01)91051-6 [pii]
AID - 10.1006/mcne.2001.1051 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2001 Dec;18(6):702-14. doi: 10.1006/mcne.2001.1051.