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Topic Review
Tauopathies
Tauopathies are neurodegenerative diseases characterized by the pathological accumulation of microtubule associated protein Tau (MAPT) in the form of neurofibrillary tangles and paired helical filaments in neurons and glia, leading to brain cell death. These diseases include frontotemporal dementia (FTD) and Alzheimer’s disease (AD) and can be sporadic or inherited when caused by mutations in the MAPT gene. Despite an incredibly high socio-economic burden worldwide, there are still no effective disease-modifying therapies and few Tau-focused experimental drugs have reached clinical trials. One major hindrance for therapeutic development is the knowledge gap in molecular mechanisms of Tau-mediated neuronal toxicity and death. For the promise of precision medicine for brain disorders to be fulfilled, it is necessary to integrate known genetic causes of disease, i.e., MAPT mutations, with understanding of the dysregulated molecular pathways that constitute potential therapeutic targets. Here, the growing understanding of known and proposed mechanisms of disease etiology will be reviewed, together with promising experimental Tau-directed therapeutics, such as recently developed Tau degraders. A particular focus will be given to the application of patient-specific stem cell models to study disease, and a number ofCurrent challenges faced by the fields of Tau research and drug discovery will alsobe addressed, including Tau pathophysiology unanswered questions, limitations of model systems and current challenges faced in developing cell-permeable small molecules that target Tau in disease.
  • 996
  • 07 Dec 2020
Topic Review
Tau protein Interaction Partners
Tau protein belongs to the family of microtubule-associated proteins (MAPs) and can influence axonal transport and growth, neuronal polarization, and thus the normal function of neurons and the brain.
  • 844
  • 15 Dec 2021
Topic Review
Tau Pathology in Alzheimer’s Disease and Down Syndrome
Individuals with Down syndrome (DS) exhibit an almost complete penetrance of Alzheimer’s disease (AD) pathology but are underrepresented in clinical trials for AD. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation of Tau (p-Tau), which may seed pathology to bystander cells and spread.
  • 265
  • 07 Mar 2024
Topic Review
Tau Oligomers Neurotoxicity
Although the mechanisms of toxic activity of tau are not fully recognized, it is supposed that the tau toxicity is related rather not to insoluble tau aggregates but to its intermediate forms. It seems that neurofibrillar tangles (NFTs) themselves, despite being composed of toxic tau, are probably neither necessary nor sufficient for tau-induced neuronal dysfunction and toxicity. Tau oligomers (TauOs) formed during the early stages of tau aggregation are the pathological forms that play a key role in eliciting the loss of neurons and behavioral impairments in several neurodegenerative disorders called tauopathies. They can be found in tauopathic diseases, the most common of which is Alzheimer’s disease (AD). Evidence of co-occurrence of b-amyloid, α-synuclein, and tau into their most toxic forms, i.e., oligomers, suggests that these species interact and influence each other’s aggregation in several tauopathies. The mechanism responsible for oligomeric tau neurotoxicity is a subject of intensive investigation.
  • 686
  • 21 Jan 2021
Topic Review
Tau Isoforms
Tau was first described as a natively unfolded microtubule-associated protein. In fact, its main function is to promote the assembly of microtubules and stabilize their structure. However, Tau proteins have a variety of other functions, which include maintaining the structural integrity of neurons, contributing to signal transmission between neurons, and axonal transport. Tau also plays a role in regulating myelination, iron homeostasis, and neurogenesis and may also support synaptic plasticity. Other roles attributed to Tau are gene expression regulation, DNA protection, genome stability, microRNA activity, RNA protection, RNA metabolism, and protein synthesis.
  • 894
  • 27 Dec 2022
Topic Review
TATDN2
Replicative DNA polymerases are blocked by nearly all types of DNA damage. The resulting DNA replication stress threatens genome stability. DNA replication stress is also caused by depletion of nucleotide pools, DNA polymerase inhibitors, and DNA sequences or structures that are difficult to replicate. Replication stress triggers complex cellular responses that include cell cycle arrest, replication fork collapse to one-ended DNA double-strand breaks, induction of DNA repair, and programmed cell death after excessive damage. Replication stress caused by specific structures (e.g., G-rich sequences that form G-quadruplexes) is localized but occurs during the S phase of every cell division.
  • 493
  • 06 Dec 2023
Topic Review
TAT Gene
Tyrosine aminotransferase: The TAT gene provides instructions for making a liver enzyme called tyrosine aminotransferase. 
  • 548
  • 24 Dec 2020
Topic Review
Taste Receptors and Sperm Biology
Taste receptors were first described as sensory receptors located on the tongue, where they are expressed in small clusters of specialized epithelial cells. Taste receptors and components of the coupled taste transduction cascade are also expressed during the different phases of spermatogenesis as well as in mature spermatozoa from mouse to humans and the overlap between the ligand spectrum of taste receptors with compounds in the male and female reproductive organs makes it reasonable to assume that sperm “taste” these different cues in their natural microenvironments. 
  • 795
  • 17 Jan 2022
Topic Review
Taste Processing from Animal Models
Taste processing is an adaptive mechanism involving complex physiological, motivational and cognitive processes. Animal models have provided relevant data about the neuroanatomical and neurobiological components of taste processing. 
  • 382
  • 30 Nov 2021
Topic Review
Taste 2 Receptors in Intestine
Taste 2 receptors (T2Rs) are G-protein-coupled receptors responsible for sensing bitter tastes. Many studies have shown the expression of T2Rs in extraoral tissues and the unique role of T2Rs in each tissue. Single-nucleotide polymorphisms of T2Rs are associated with the risk of obesity and diabetes, and the organs/tissues associated with the development of these metabolic diseases, including the intestine, adipose, muscle, liver, and pancreas, are reported to express T2R genes. This result suggests that T2Rs in extraoral tissues contribute to the development of obesity and diabetes.
  • 388
  • 14 Dec 2023
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