Regulation of human MAPT gene expression

Caillet-Boudin, Marie-Laure; Buée, Luc; Lefebvre, Bruno

doi:10.1186/s13024-015-0025-8

Cited by 153 publications

(134 citation statements)

References 165 publications

Supporting

Mentioning

122

Contrasting

Unclassified

Order By: Relevance

“…The six main isoforms of tau in the adult brain result in varying affinities for microtubules, so splicing events may play a role in the propensity for aggregation in tauopathies (53). Pathological tau can cause disturbances of microtubules leading to neuronal degeneration, and aggregated tau is cytotoxic.…”

Section: Neurofibrillary Tangles As Drug Targetsmentioning

confidence: 99%

Update on Alzheimer's Disease Therapy and Prevention Strategies

2017

View full text Add to dashboard Cite

Alzheimer's disease (AD) is the primary cause of age-related dementia. Effective strategies to prevent and treat AD remain elusive despite major efforts to understand its basic biology and clinical pathophysiology. Significant investments in therapeutic drug discovery programs over the past two decades have yielded some important insights but no blockbuster drugs to alter the course of disease. Because significant memory loss and cognitive decline are associated with neuron death and loss of gray matter, especially in the frontal cortex and hippocampus, some focus in drug development has shifted to early prevention of cellular pathology. Although clinical trial design is challenging, due in part to a lack of robust biomarkers with predictive value, some optimism has come from the identification and study of inherited forms of early-onset AD and genetic risk factors that provide insights about molecular pathophysiology and potential drug targets. In addition, better understanding of the Aβ amyloid pathway and the tau pathway-leading to amyloid plaques and neurofibrillary tangles, respectively, which are histopathological hallmarks of AD-continues to drive significant drug research and development programs. The main focus of this review is to summarize the most recent basic biology, biochemistry, and pharmacology that serve as a foundation for more than 50 active advanced-phase clinical trials for AD prevention and therapy.

show abstract

Section: Neurofibrillary Tangles As Drug Targetsmentioning

confidence: 99%

Update on Alzheimer's Disease Therapy and Prevention Strategies

2017

View full text Add to dashboard Cite

show abstract

“…There are approximately thirty known tauopathies, with different clinical, pathological and biological characteristics (Caillet-Boudin et al, 2015). Some tauopathies are considered familial and are related to precise mutations of the tau gene, while others are sporadic in nature with no direct genetic links.…”

Section: Introductionmentioning

confidence: 99%

Developmental exposure to lead (Pb) alters the expression of the human tau gene and its products in a transgenic animal model

et al. 2016

View full text Add to dashboard Cite

Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregationof the tau protein in the human brain. The best known of these illnesses is Alzheimer's disease (AD); a disease where the microtubule associated protein tau (MAPT) becomes hyperphosphorylated (lowering its binding affinity to microtubules) and aggregates within neurons in the form of neurofibrillary tangles (NFTs). In this paper we examine whether environmental factors play a significant role in tau pathogenesis. Our studies were conducted in a double mutant mouse model that expressed the human tau gene and lacked the gene for murine tau. The human tau mouse model was tested for the transgene's ability to respond to an environmental toxicant. Pups were developmentally exposed to lead (Pb) from postnatal day (PND) 1-20 with 0.2% Pb acetate. Mice were then sacrificed at PND 20, 30, 40 and 60. Protein and mRNA levels for tau and CDK5 as well as tau phosphorylation at Ser396 were determined. In addition, the potential role of miRNA in tau expression was investigated by measuring levels of miR-34c, a miRNA that targets the mRNA for human tau, at PND20 and 50. The expression of the human tau transgene was altered by developmental exposure to Pb. This exposure also altered the expression of miR-34c. Our findings are the first of their kind to test the responsiveness of the human tau gene to an environmental toxicant and to examine an epigenetic mechanism that may be involved in the regulation of this gene's expression.

show abstract

“…Tau protein is expressed mainly in the human brain as 6 isoforms, generated by alternative splicing [70, 71]. Tau belongs to the microtubule-associated proteins (MAPs) family which includes MAP2 and MAP4 [72] and is well known for its role in microtubule assembly and stability, playing a role in diverse cellular processes such as cell morphogenesis, cell division, and intracellular trafficking.…”

Section: Overview On Tau and Tauopathiesmentioning

confidence: 99%

Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

et al. 2018

Self Cite

View full text Add to dashboard Cite

Alzheimer disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments, and lower brain glucose metabolism, which often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood. Insulin is a hormone involved in the control of energy homeostasis both peripherally and centrally, and insulin-resistant state has been linked to increased risk of dementia. It is now well established that insulin resistance can exacerbate Tau lesions, mainly by disrupting the balance between Tau kinases and phosphatases. On the other hand, the emerging literature indicates that Tau protein can also modulate insulin signalling in the brain, thus creating a detrimental vicious circle. The following review will highlight our current understanding of the role of insulin in the brain and its relation to Tau protein in the context of AD and tauopathies. Considering that insulin signalling is prone to be pharmacologically targeted at multiple levels, it constitutes an appealing approach to improve both insulin brain sensitivity and mitigate brain pathology with expected positive outcome in terms of cognition.

show abstract

Regulation of human MAPT gene expression

Cited by 153 publications

References 165 publications

Update on Alzheimer's Disease Therapy and Prevention Strategies

Update on Alzheimer's Disease Therapy and Prevention Strategies

Developmental exposure to lead (Pb) alters the expression of the human tau gene and its products in a transgenic animal model

Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

Contact Info

Product

Resources

About