PMID- 9836646
OWN - NLM
STAT- MEDLINE
DCOM- 19981228
LR  - 20220318
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 282
IP  - 5395
DP  - 1998 Dec 4
TI  - Mutation-specific functional impairments in distinct tau isoforms of hereditary 
      FTDP-17.
PG  - 1914-7
AB  - Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative 
      diseases, including Alzheimer's disease and hereditary frontotemporal dementia 
      and parkinsonism linked to chromosome 17 (FTDP-17). Over 10 exonic and intronic 
      mutations in the tau gene have been identified in about 20 FTDP-17 families. 
      Analyses of soluble and insoluble tau proteins from brains of FTDP-17 patients 
      indicated that different pathogenic mutations differentially altered distinct 
      biochemical properties and stoichiometry of brain tau isoforms. Functional assays 
      of recombinant tau proteins with different FTDP-17 missense mutations implicated 
      all but one of these mutations in disease pathogenesis by reducing the ability of 
      tau to bind microtubules and promote microtubule assembly.
FAU - Hong, M
AU  - Hong M
AD  - Center for Neurodegenerative Disease Research, Department of Pathology and 
      Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 
      PA 19104, USA.
FAU - Zhukareva, V
AU  - Zhukareva V
FAU - Vogelsberg-Ragaglia, V
AU  - Vogelsberg-Ragaglia V
FAU - Wszolek, Z
AU  - Wszolek Z
FAU - Reed, L
AU  - Reed L
FAU - Miller, B I
AU  - Miller BI
FAU - Geschwind, D H
AU  - Geschwind DH
FAU - Bird, T D
AU  - Bird TD
FAU - McKeel, D
AU  - McKeel D
FAU - Goate, A
AU  - Goate A
FAU - Morris, J C
AU  - Morris JC
FAU - Wilhelmsen, K C
AU  - Wilhelmsen KC
FAU - Schellenberg, G D
AU  - Schellenberg GD
FAU - Trojanowski, J Q
AU  - Trojanowski JQ
FAU - Lee, V M
AU  - Lee VM
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Protein Isoforms)
RN  - 0 (Recombinant Proteins)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Alternative Splicing
MH  - Brain/*metabolism
MH  - Cerebellum/metabolism
MH  - Chromosomes, Human, Pair 17
MH  - Dementia/*genetics/metabolism
MH  - Frontal Lobe/metabolism
MH  - Humans
MH  - Microtubules/*metabolism
MH  - Mutation
MH  - Mutation, Missense
MH  - Parkinson Disease, Secondary/*genetics/metabolism
MH  - Phosphorylation
MH  - Protein Isoforms/chemistry/genetics/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Solubility
MH  - Syndrome
MH  - tau Proteins/chemistry/*genetics/*metabolism
EDAT- 1998/12/04 00:00
MHDA- 1998/12/04 00:01
CRDT- 1998/12/04 00:00
PHST- 1998/12/04 00:00 [pubmed]
PHST- 1998/12/04 00:01 [medline]
PHST- 1998/12/04 00:00 [entrez]
AID - 10.1126/science.282.5395.1914 [doi]
PST - ppublish
SO  - Science. 1998 Dec 4;282(5395):1914-7. doi: 10.1126/science.282.5395.1914.