Tauopathies

Neurodegenerative disorders involving deposition of abnormal tau protein isoforms (TAU PROTEINS) in neurons and glial cells in the brain. Pathological aggregations of tau proteins are associated with mutation of the tau gene on chromosome 17 in patients with ALZHEIMER DISEASE; DEMENTIA; PARKINSONIAN DISORDERS; progressive supranuclear palsy (SUPRANUCLEAR PALSY, PROGRESSIVE); and corticobasal degeneration.

Also Known As:

Networked: 952 relevant articles (31 outcomes, 85 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Alzheimer Disease (Alzheimer's Disease)
2.	Tauopathies
3.	Parkinson Disease (Parkinson's Disease)
4.	Frontotemporal Lobar Degeneration (Semantic Dementia)
5.	Frontotemporal Dementia

Experts

1.	Trojanowski, John Q: 42 articles (01/2015 - 05/2002)
2.	Lee, Virginia M-Y: 42 articles (01/2015 - 06/2002)
3.	Novak, Michal: 22 articles (01/2016 - 08/2006)
4.	Goedert, Michel: 21 articles (09/2014 - 03/2002)
5.	Van Leuven, Fred: 19 articles (07/2014 - 02/2005)
6.	Dickey, Chad A: 17 articles (11/2015 - 10/2006)
7.	Borghgraef, Peter: 17 articles (07/2014 - 02/2005)
8.	Avila, Jesús: 16 articles (01/2016 - 03/2002)
9.	Iqbal, Khalid: 16 articles (04/2015 - 08/2002)
10.	Buée, Luc: 15 articles (12/2015 - 01/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Tauopathies:

1.	tau Proteins (tau Protein)IBA 01/01/2014 - "Suppression of tau protein expression has been shown to improve behavioral deficits in mouse models of tauopathies, offering an attractive therapeutic approach. " 06/01/2013 - "Previous studies identified EFhd2 associated with pathological forms of tau proteins in the tauopathy mouse model JNPL3, which expresses the human tau(P301L) mutant. " 12/14/2012 - "This study demonstrates that cells actively release Tau in the absence of disease or toxicity, and Tau release is modified by changes in the Tau protein that are associated with tauopathies." 02/01/2011 - "Because murine tau might interfere with the toxic effects of human mutant tau, we generated a model in which a pathogenic human tau protein is expressed in the absence of wild-type tau protein, with the aim of facilitating the study of the pathogenic role of the mutant tau and to reproduce more faithfully a human tauopathy. " 05/01/2010 - "To address the determinants of Tau neurotoxicity, we used Drosophila models of human tauopathies to study the microtubule-binding properties of human Tau proteins in vivo. "
2.	Proteins (Proteins, Gene)IBA 05/01/2005 - "Some proteins are quite useful for discovering the molecular mechanisms of tauopathies and may be helpful for diagnosis and of treatment tauopathies." 05/01/2005 - "Comparative proteomic analysis of brain proteins was employed to study 4 patients with tauopathies as compared with 4 controls. " 09/01/2014 - "To uncover proteins involved in the development of tauopathies, a yeast two-hybrid system was used to screen for tau-interacting proteins. " 07/18/2014 - "Increasingly, it appears that misfolded proteins in Alzheimer and Parkinson diseases and the tauopathies also propagate in a "prion-like" manner. " 11/14/2012 - "Here, a proteomics approach was used to identify proteins that may be affected during the course of tau-mediated neurodegeneration in the tauopathy mouse model JNPL3. "
3.	Amyloid (Amyloid Fibrils)IBA 01/01/2011 - "To investigate whether the mechanism of in vitro neuroprotection relates to the in vivo protection against tauopathy and to draw potential additional parallelism between NAP and D-SAL, we asked if: 1]NAP and D-SAL protect against amyloid beta related tau hyperphosphorylation in vitro; and 2] D-SAL protects against haploinsufficiency in ADNP, inhibiting tauopathy in vivo. " 01/01/2015 - "In broader terms, our study provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer's, Parkinson's, and tauopathies." 01/01/2014 - "Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (Aβ) deposits, tauopathy, and neuroinflammation. " 06/12/2015 - "Tau amyloid assemblies propagate aggregation from the outside to the inside of a cell, which may mediate progression of the tauopathies. " 04/01/2015 - "Finally, we discussed the possible impact of CR1 on the pathogenesis of AD including amyloid-β pathology, tauopathy, immune dysfunction and glial-mediated neuroinflammation. "
4.	LithiumIBA 01/01/2013 - "Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. " 04/01/2012 - "Long-term oral lithium treatment attenuates motor disturbance in tauopathy model mice: implications of autophagy promotion." 03/21/2008 - "Lithium has been also reported to protect cultured neurons against Abeta toxicity, and to prevent NFTs accumulation and cognitive impairments in transgenic models of tauopathies. " 12/01/2006 - "Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. " 12/01/2005 - "These findings suggest novel mechanisms whereby lithium treatment could ameliorate tauopathies including AD. "
5.	IronIBA 03/01/2013 - "The relative lack of tauopathy and the presence of p62-positive glial inclusions or iron-positive pigments in the pallidonigroluysian region may help to distinguish pallidonigroluysian atrophy from similar disease entities." 02/01/2012 - "These data suggest that the loss of soluble tau could contribute to toxic neuronal iron accumulation in Alzheimer's disease, Parkinson's disease and tauopathies, and that it can be rescued pharmacologically." 02/01/2012 - "Neuronal iron accumulation has been observed pathologically in the cortex in Alzheimer's disease, the substantia nigra (SN) in Parkinson's disease and various brain regions in the tauopathies. " 08/01/2015 - "Compelling data indicated that PICALM affects AD risk primarily by modulating production, transportation, and clearance of β-amyloid (Aβ) peptide, but other Aβ-independent pathways are discussed, including tauopathy, synaptic dysfunction, disorganized lipid metabolism, immune disorder, and disrupted iron homeostasis. "
6.	Phosphotransferases (Kinase)IBA 07/26/2013 - "Given the contribution of both CDK5/p25 and GSK3β to Tau phosphorylation, effective treatment of tauopathies may require dual kinase targeting. " 09/01/2014 - "Here, we determine whether Cdk5, a hyperactivated kinase in tauopathies, phosphorylates EFhd2 and influence its known molecular activities. " 08/09/2013 - "The findings identify novel tau kinases and novel pathways that may be relevant for AD and other tauopathies. " 01/01/2009 - "Here, we employed a well-characterized Drosophila model of tauopathy to investigate the interdependence of tau kinases in regulating the phosphorylation and toxicity of tau in vivo. " 12/01/2007 - "Kinase activities increase during the development of tauopathy in htau mice."
7.	Biological Markers (Surrogate Marker)IBA 01/01/2013 - "Our results suggested that addition of the two-OR biomarker model to current diagnostic criteria may lead to improved TBI detection for clinical trials, and decreased expression of OR TBI biomarkers might be associated with TBI-induced tauopathy. " 01/01/2016 - "Imaging biomarkers in tauopathies." 11/01/2015 - "Our data suggest that [F-18]-AV-1451 holds promise as a surrogate marker for the detection of brain tau pathology in the form of tangles and paired helical filament-tau-containing neurites in Alzheimer brains but also point to its relatively lower affinity for lesions primarily made of straight tau filaments in non-Alzheimer tauopathy cases and to the existence of some [F-18]-AV-1451 off-target binding. " 07/01/2011 - "Now several modalities like functional magnetic resonance imaging (fMRI), positron emission tomography (PET) scan, electrophysiological tests and cerebrospinal fluid (CSF) biomarkers for tauopathy and Aβ have shown to be promising in the development of early diagnostic tools for neurodegenerative changes and help us to differentiate between healthy aging and pathological aging. " 06/01/2010 - "The increase in the CSF level of p-tau(181) during progressive behavioural decline suggests that it may represent a useful surrogate biomarker for preclinical drug development and a potential surrogate endpoint for clinical trials of disease-modifying therapy for Alzheimer's disease and related human tauopathies."
8.	alpha-SynucleinIBA 09/01/2009 - "Previous immunohistochemical studies in a small number of PEP cases demonstrated absence of Lewy bodies as well as the lack of other alpha-synuclein pathology, classifying PEP as a "pure" tauopathy. " 07/01/2000 - "Thus, the present study suggests that a common mechanism may govern aggregation of alpha-synuclein and tau in the amygdala, and that aggregation of alpha-synuclein may play some role in the neurodegenerative process of a tauopathy (i.e. " 09/01/2009 - "The causes and molecular background of total absence of alpha-synuclein pathology in PEP, in contrast to most other tauopathies, remain as unknown as the pathogenesis of PEP." 07/01/2007 - "The Abeta peptide patterns varied between tauopathies and synucleinopathies and between all diseases and the comparison group, possibly due to the influence of tau and alpha-synuclein on Abeta-processing." 08/01/2004 - "Now we can see a striking resemblance between alpha-synuclein and tau: both have the same physiological function and pathological features, making abnormal structures in diseased brains known as synucleinopathies and tauopathies. "
9.	PeptidesIBA 01/01/2014 - "Active immunization using tau phospho-peptides in tauopathy mouse models has been observed to reduce tau pathology, especially when given prior to the onset of pathology. " 08/01/2014 - "Previous studies have also linked the autophagy-lysosomal pathway to the protective clearing of the Aβ peptides of Alzheimer's disease and tau species of tauopathies. " 12/01/2014 - "Dysregulation of the splicing process of tau exon 10 is sufficient to cause tauopathy and has shown to be influenced by beta-amyloid peptides, but splicing of other exons is less studied. " 11/03/2010 - "The prevailing pathogenic theory, the "amyloid cascade hypothesis" (Hardy and Selkoe, 2002), posits that the accumulation of amyloidogenic peptides triggers tauopathy, neurodegeneration, and cognitive and behavioral changes. " 07/01/2007 - "Tauopathies and synucleinopathies: do cerebrospinal fluid beta-amyloid peptides reflect disease-specific pathogenesis?"
10.	NAPVSIPQ peptideIBA 01/01/2011 - "Protection against tauopathy by the drug candidates NAP (davunetide) and D-SAL: biochemical, cellular and behavioral aspects." 07/01/2013 - "NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy." 11/01/2012 - "ADNP haploinsufficiency in mice results in tauopathy and cognitive deficits ameliorated by davunetide treatment. " 11/01/2012 - "Davunetide (NAP) is a leading drug candidate being tested against tauopathy. " 01/01/2011 - "In conclusion, NAP (davunetide) provided potent neuroprotection in a broad range of neurodegenerative models, protecting the neuroglial cytoskeleton in vitro and inhibiting tau pathology (tauopathy) in vivo. "

Therapies and Procedures

1.	Immunotherapy 01/01/2015 - "These studies provide evidence supporting the use of tau immunotherapy as a potential treatment option for AD and other tauopathies. " 01/01/2014 - "In this report, we present our discovery of (1) a novel target for tau immunotherapy; (2) monoclonal antibody DC8E8, which neutralizes this target; and (3) the results of efficacy studies of DC8E8 in a murine model of tauopathy. " 12/08/2010 - "Overall, our findings indicate that immunotherapy targeting pathological tau is very feasible for tauopathies, and should be assessed in clinical trials in the near future." 01/01/2014 - "Over 12 years ago, we initiated a tau immunotherapy program, seeking to alleviate the functional impairments associated with tau lesions in tauopathies. " 10/16/2013 - "Immunotherapies targeting tau in mouse models of human tauopathies could have disease-modifying effects. "
2.	Therapeutics 11/01/2007 - "The molecular basis of chaperone-mediated protection against neurodegeneration might lead to the development of therapeutics for tauopathies. " 01/01/2013 - "Finding therapeutics to reverse or remove this non-native tau state is of great interest; however, at this time only one drug is entering phase III clinical trials for treating tauopathies. " 02/01/2015 - "Together, our data indicate that silencing of tau by miR-219 is an ancient regulatory mechanism that may become perturbed during neurofibrillary degeneration and suggest that this regulatory pathway may be useful for developing therapeutics for tauopathies. " 01/01/2015 - "Herein, we highlight the various causes of tauopathy and HSP-E3 ligase mediated therapeutics in AD. " 09/17/2014 - "Advances in therapeutics for neurodegenerative tauopathies: moving toward the specific targeting of the most toxic tau species."
3.	Anesthesia 08/01/2009 - "Interestingly, the level of insoluble tau was increased 1 wk following anesthesia, suggesting that anesthesia precipitates changes in the brain that provoke the later development of tauopathy. " 08/01/2009 - "To investigate whether anesthesia enhances the long-term risk of developing pathological forms of tau, we exposed a mouse model with tauopathy to anesthesia and monitored the outcome at two time points-during anesthesia, or 1 wk after exposure. " 08/01/2009 - "Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia." 04/01/2012 - "We now report that isoflurane anesthesia in young, pre-symptomatic Tau.P301L mice triggered precocious upper airways defects and tauopathy in several brainstem nuclei, including the nucleus ambiguus that contains upper airways motor neurons and the Kolliker-Fuse. " 04/01/2012 - "Isoflurane anesthesia precipitates tauopathy and upper airways dysfunction in pre-symptomatic Tau.P301L mice: possible implication for neurodegenerative diseases."
4.	Individualized Medicine 06/01/2010 - "The current manuscript touches on the variability as well as common denominators of the various tau pathologies coupled to new approaches/current innovation in treatment of tauopathies in favor of advanced technologies in predictive diagnostics, targeted preventive and personalized medicine (PPPM)."
5.	Tissue Therapy (Cell Therapy) 10/13/2011 - "We suggest that cell therapy may represent an alternative therapeutic avenue for treatment of human Alzheimer's disease and related tauopathies."