Last update 01 Nov 2024

AR x TAU

Last update 01 Nov 2024

Basic Info

Related Targets

ARTAU

Drugs associated with AR x TAU

ADEL-Y07

Target

AR x TAU

Mechanism

AR antagonists [+1]

Active Org.

ADEL, Inc.

Originator Org.

ADEL, Inc.

Active Indication

Alzheimer Disease [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with AR x TAU

100 Translational Medicine associated with AR x TAU

0 Patents (Medical) associated with AR x TAU

Literatures (Medical) associated with AR x TAU

01 Apr 2024·Current Drug Targets

Molecular Targets and Mechanisms of Hedyotis diffusa Willd. for Esophageal Adenocarcinoma Treatment Based on Network Pharmacology and Weighted Gene Co-expression Network Analysis

Article

Author: Shao, Feng ; Che, Chao ; Zhang, Qiang ; Sun, Yun-Gang ; Wang, Chen-Guang ; Zhuang, Yu

Background::Hedyotis diffusa Willd. (HDW) is a common anticancer herbal medicine in China, and its therapeutic effectiveness has been demonstrated in a range of cancer patients. There is no consensus about the therapeutic targets and molecular mechanisms of HDW, which contains many active ingredients.Aim::To clarify the mechanism of HDW for esophageal adenocarcinoma (EAC), we utilized network pharmacology and weighted gene co-expression network analysis methods (WGCNA).Methods::The gene modules that were linked with the clinical features of EAC were obtained through the WGCNA method. Then, the potential target genes were retrieved through the network pharmacology method in order to determine the targets of the active components. After enrichment analysis, a variety of signaling pathways with significant ratios of target genes were found, including regulation of trans-synaptic signaling, neuroactive ligand-receptor interaction and modulation of chemical synaptic transmission. By means of protein-protein interaction (PPI) network analysis, we have successfully identified the hub genes, which were AR, CNR1, GRIK1, MAPK10, MAPT, PGR and PIK3R1.Result::Our study employed molecular docking simulations to evaluate the binding affinity of the active components with the hub gene. The identified active anticancer constituents in HDW are scopoletol, quercetin, ferulic acid, coumarin, and trans-4-methoxycinnamyl alcohol.Conclusion::Our findings shed light on the molecular underpinnings of HDW in the treatment of EAC and hold great promise for the identification of potential HDW compounds and biomarkers for EAC therapy.

01 Mar 2024·iScience

Location of the axon initial segment assembly can be predicted from neuronal shape

Article

Author: Xu, Zhuang ; Wu, Yuhuang ; Curmi, Paul M G ; Stefen, Holly ; Angstmann, Christopher N ; Fath, Thomas ; Parić, Esmeralda

The axon initial segment (AIS) is located at the proximal axon demarcating the boundary between axonal and somatodendritic compartments. The AIS facilitates the generation of action potentials and maintenance of neuronal polarity. In this study, we show that the location of AIS assembly, as marked by Ankyrin G, corresponds to the nodal plane of the lowest-order harmonic of the Laplace-Beltrami operator solved over the neuronal shape. This correlation establishes a coupling between location of AIS assembly and neuronal cell morphology. We validate this correlation for neurons with atypical morphology and neurons containing multiple AnkG clusters on distinct neurites, where the nodal plane selects the appropriate axon showing enriched Tau. Based on our findings, we propose that Turing patterning systems are candidates for dynamically governing AIS location. Overall, this study highlights the importance of neuronal cell morphology in determining the precise localization of the AIS within the proximal axon.

01 Jan 2023·Journal of Alzheimer's disease : JAD

Extracellular Tau Oligomers Damage the Axon Initial Segment.

Article

Author: Bloom, George S ; Lim, Yunu ; Sharifi, Kamyar ; Mandell, James W ; Jones, Marieke K ; Min, Lia ; Kim, Nayoung ; McTavish, Sloane A ; Best, Merci N ; Wang, Dora Bigler ; Siller, Karsten H ; Ferenc, Nina N ; Jenkins, Paul M ; Wasserman, Anna E

BACKGROUNDIn Alzheimer's disease (AD) brain, neuronal polarity and synaptic connectivity are compromised. A key structure for regulating polarity and functions of neurons is the axon initial segment (AIS), which segregates somatodendritic from axonal proteins and initiates action potentials. Toxic tau species, including extracellular oligomers (xcTauOs), spread tau pathology from neuron to neuron by a prion-like process, but few other cell biological effects of xcTauOs have been described.OBJECTIVETest the hypothesis that AIS structure is sensitive to xcTauOs.METHODSCultured wild type (WT) and tau knockout (KO) mouse cortical neurons were exposed to xcTauOs, and quantitative western blotting and immunofluorescence microscopy with anti-TRIM46 monitored effects on the AIS. The same methods were used to compare TRIM46 and two other resident AIS proteins in human hippocampal tissue obtained from AD and age-matched non-AD donors.RESULTSWithout affecting total TRIM46 levels, xcTauOs reduce the concentration of TRIM46 within the AIS and cause AIS shortening in cultured WT, but not TKO neurons. Lentiviral-driven tau expression in tau KO neurons rescues AIS length sensitivity to xcTauOs. In human AD hippocampus, the overall protein levels of multiple resident AIS proteins are unchanged compared to non-AD brain, but TRIM46 concentration within the AIS and AIS length are reduced in neurons containing neurofibrillary tangles.CONCLUSIONxcTauOs cause partial AIS damage in cultured neurons by a mechanism dependent on intracellular tau, thereby raising the possibility that the observed AIS reduction in AD neurons in vivo is caused by xcTauOs working in concert with endogenous neuronal tau.

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