PMID- 18625456
OWN - NLM
STAT- MEDLINE
DCOM- 20081105
LR  - 20240204
IS  - 1933-7213 (Print)
IS  - 1878-7479 (Electronic)
IS  - 1878-7479 (Linking)
VI  - 5
IP  - 3
DP  - 2008 Jul
TI  - Tau-based treatment strategies in neurodegenerative diseases.
PG  - 443-57
LID - 10.1016/j.nurt.2008.05.006 [doi]
AB  - Neurofibrillary tangles are a characteristic hallmark of Alzheimer's and other 
      neurodegenerative diseases, such as Pick's disease (PiD), progressive 
      supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal 
      dementia and parkinsonism linked to chromosome 17 (FTDP-17). These diseases are 
      summarized as tauopathies, because neurofibrillary tangles are composed of 
      intracellular aggregates of the microtubule-associated protein tau. The molecular 
      mechanisms of tau-mediated neurotoxicity are not well understood; however, 
      pathologic hyperphosphorylation and aggregation of tau play a central role in 
      neurodegeneration and neuronal dysfunction. The present review, therefore, 
      focuses on therapeutic approaches that aim to inhibit tau phosphorylation and 
      aggregation or to dissolve preexisting tau aggregates. Further experimental 
      therapy strategies include the enhancement of tau clearance by activation of 
      proteolytic, proteasomal, or autophagosomal degradation pathways or anti-tau 
      directed immunotherapy. Hyperphosphorylated tau does not bind microtubules, 
      leading to microtubule instability and transport impairment. Pharmacological 
      stabilization of microtubule networks might counteract this effect. In several 
      tauopathies there is a shift toward four-repeat tau isoforms, and interference 
      with the splicing machinery to decrease four-repeat splicing might be another 
      therapeutic option.
FAU - Schneider, Anja
AU  - Schneider A
AD  - Department of Psychiatry and Psychotherapy, Von-Siebold-Strasse 5, University of 
      Goettingen, Goettingen, Germany.
FAU - Mandelkow, Eckhard
AU  - Mandelkow E
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Neurotherapeutics
JT  - Neurotherapeutics : the journal of the American Society for Experimental 
      NeuroTherapeutics
JID - 101290381
RN  - 0 (Antibodies)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies/*therapeutic use
MH  - Brain/metabolism/pathology
MH  - Humans
MH  - Immunotherapy
MH  - Models, Biological
MH  - Neurodegenerative Diseases/genetics/*metabolism/pathology/*therapy
MH  - Neurofibrillary Tangles/metabolism/pathology
MH  - tau Proteins/*immunology/*metabolism
PMC - PMC5084246
EDAT- 2008/07/16 09:00
MHDA- 2008/11/06 09:00
PMCR- 2009/07/01
CRDT- 2008/07/16 09:00
PHST- 2008/07/16 09:00 [pubmed]
PHST- 2008/11/06 09:00 [medline]
PHST- 2008/07/16 09:00 [entrez]
PHST- 2009/07/01 00:00 [pmc-release]
AID - S1878-7479(23)00494-4 [pii]
AID - 50300443 [pii]
AID - 10.1016/j.nurt.2008.05.006 [doi]
PST - ppublish
SO  - Neurotherapeutics. 2008 Jul;5(3):443-57. doi: 10.1016/j.nurt.2008.05.006.