Results 41 to 50 of about 19,325 (262)

Allosteric Modulation of Muscarinic Acetylcholine Receptors [PDF]

Current Neuropharmacology, 2007
Muscarinic acetylcholine receptors (mAChRs) are prototypical Family A G protein coupled-receptors. The five mAChR subtypes are widespread throughout the periphery and the central nervous system and, accordingly, are widely involved in a variety of both physiological and pathophysiological processes.
Gregory, Karen J, Sexton, Patrick M, Christopoulos, Arthur   +2 more
openaire   +2 more sources

Valosin‐containing protein counteracts ATP‐driven dissolution of FUS condensates through its ATPase activity in vitro

FEBS Letters, EarlyView.
Biomolecular condensates formed by fused in sarcoma (FUS) are dissolved by high ATP concentrations yet persist in cells. Using a reconstituted system, we demonstrate that valosin‐containing protein (VCP), an AAA+ ATPase, counteracts ATP‐driven dissolution of FUS condensates through its D2 ATPase activity.
Hitomi Kimura, Shin‐ichi Tate, Kyota Yasuda   +2 more
wiley   +1 more source

A Silent Allosteric Modulator

Molecular Medicine Communications, 2022
Deterioration in cognitive dysfunction in Alzheimer’s disease (AD) patients is associated with microglia-mediated synaptic destruction. Using AD mouse models Spurrier and colleagues discerned the function of the metabotropic glutamate receptor 5 (mGluR5) on synaptic loss and demonstrated that a silent allosteric modulator (SAM) of mGLuR5 when given ...
openaire   +1 more source

Allosteric Modulators Hit the TSH Receptor [PDF]

Endocrinology, 2014
The receptor for TSH (TSHR) has captured our interest and imagination since it was first demonstrated to be a major human antigen in autoimmune thyroid disease. The original realization that the immunoglobulin fraction of sera from patients with Graves' disease incorporated unique human autoantibodies to the TSHR led to the unraveling of the great ...
Terry F, Davies, M Rejwan, Ali, Rauf, Latif   +2 more
openaire   +2 more sources

Potential therapeutic targeting of BKCa channels in glioblastoma treatment

Molecular Oncology, EarlyView.
This review summarizes current insights into the role of BKCa and mitoBKCa channels in glioblastoma biology, their potential classification as oncochannels, and the emerging pharmacological strategies targeting these channels, emphasizing the translational challenges in developing BKCa‐directed therapies for glioblastoma treatment.
Kamila Maliszewska‐Olejniczak, Karolina Pytlak, Sandra Jaworowska, Bogusz Kulawiak, Piotr Bednarczyk   +4 more
wiley   +1 more source

Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia

Nature Communications, 2023
TRPV1 as a drug target suffers from side effects of hypothermia. Here, authors engineer a peptide, sRhTx, as a positive allosteric modulator of TRPV1 channel. It potentiates the activity of TRPV1 to reversibly ablate pain-sensing nerve terminals for long-
Heng Zhang, Jia-Jia Lin, Ya-Kai Xie, Xiu-Zu Song, Jia-Yi Sun, Bei-Lei Zhang, Yun-Kun Qi, Zhen-Zhong Xu, Fan Yang   +8 more
doaj   +1 more source

Allosteric modulators targeting CNS muscarinic receptors [PDF]

Neuropharmacology, 2018
Muscarinic acetylcholine receptors are G protein-coupled receptors (GPCRs) which are broadly expressed in the central nervous system (CNS) and other tissues in the periphery. They emerge as important drug targets for a number of diseases including Alzheimer's disease, Parkinson's disease, and schizophrenia.
Andreas Bock, Ramona Schrage, Klaus Mohr
openaire   +2 more sources

IMPDH inhibition enhances cytarabine efficacy in SAMHD1‐expressing leukaemia cells via guanine nucleotide depletion

Molecular Oncology, EarlyView.
Cytarabine is a key therapy for acute myeloid leukaemia (AML), but its efficacy is limited by the dNTPase SAMHD1, which hydrolyses its active metabolite. Screening nucleotide biosynthesis inhibitors revealed that IMPDH inhibitors selectively sensitise SAMHD1‐proficient AML cells to cytarabine.
Miriam Yagüe‐Capilla, Christopher Dirks, Caroline Eiden, Sonja K. Fesenmayer, Femke M. Hormann, Yolande Klootsema, Ingrid Lilienthal, Si Min Zhang, Nikolas Herold, Sean G. Rudd   +9 more
wiley   +1 more source

Analysing the significance of small conformational changes and low occupancy states in serial crystallographic data

FEBS Open Bio, EarlyView.
This protocol paper outlines methods to establish the success of a time‐resolved serial crystallographic experiment, by means of statistical analysis of timepoint data in reciprocal space and models in real space. We show how to amplify the signal from excited states to visualise structural changes in successful experiments.
Jake Hill, Yelyzaveta Pulnova, Elke De Zitter, Helen M. Ginn, Briony A. Yorke   +4 more
wiley   +1 more source

Positive or negative allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) does not alter expression of behavioral sensitization to methamphetamine [v1; ref status: indexed, http://f1000r.es/o0]

F1000Research, 2013
We investigated the role of metabotropic glutamate receptor type 5 (mGluR5) in methamphetamine-induced behavioral sensitization. The mGluR5 positive allosteric modulator (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) and negative allosteric ...
Peter R Kufahl, Natali E Nemirovsky, Lucas R Watterson, Nicholas Zautra, M Foster Olive   +4 more
doaj   +1 more source