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Background: Loss of medullary serotonin (5-hydroxytryptamine) neurons has been linked to respiratory disturbances in multiple system atrophy (MSA). Broader 5-hydroxytryptamine dysfunction may contribute to additional motor/nonmotor symptoms in MSA. The objective of this study was to compare brain 5-hydroxytryptamine receptor binding between MSA and healthy controls. Secondary objectives were to compare 5-hydroxytryptamine receptor binding between MSA and Parkinson's disease (PD) and to assess potential associations with motor/nonmotor symptoms in MSA.
Methods: 2'-Methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine positron emission tomography was performed in matched MSA patients (n = 16), PD patients (n = 15), and healthy controls (n = 18).
Results: 2'-Methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine distribution volume ratios were lower in MSA patients versus healthy controls in several brain regions including the caudate, raphe nuclei, thalamus, and brain stem. Distribution volume ratios were also lower in brain stem and amygdala in MSA versus PD. Moderate associations were found between 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine distribution volume ratios and fatigue, pain, and apathy in MSA.
Conclusion: Our results demonstrate 5-hydroxytryptamine dysfunction in several brain regions in MSA, which may contribute to fatigue, pain, and apathy. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28295 | DOI Listing |
Acta Pharmacol Sin
September 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Chemotherapeutic resistance is a significant issue in the treatment of breast cancer, which is related to pyroptosis inhibition. Increasing evidence suggests that long non-coding RNAs (lncRNAs) contribute to tumorigenesis and drug resistance. In this study we investigated the role of the lncRNA STMN1P2 in doxorubicin resistance in breast cancer, as well as its correlation with pyroptosis inhibition.
View Article and Find Full Text PDFNat Chem Biol
September 2025
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Many pharmaceutical targets partition into biomolecular condensates, whose microenvironments can significantly influence drug distribution. Nevertheless, it is unclear how drug design principles should adjust for these targets to optimize target engagement. To address this question, we systematically investigated how condensate microenvironments influence drug-targeting efficiency.
View Article and Find Full Text PDFZhonghua Jie He He Hu Xi Za Zhi
September 2025
Department of nursing, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are important treatments for EGFR mutant non-small cell lung cancer (NSCLC). However, the first and second generation EGFR-TKI face clinical limitations due to acquired resistance, such as the T790M mutation. Irreversible EGFR-TKI can significantly prolong the survival of patients by enhancing the inhibition of drug-resistant mutations through the covalent binding mechanism.
View Article and Find Full Text PDFAnal Chem
September 2025
Department of Chemistry, Lehigh University, 6 East Packer Avenue, Bethlehem, Pennsylvania 18015, United States.
Reactive oxygen species (ROS) are responsible for the oxidative truncation of polyunsaturated fatty acids (PUFAs). The products of these reactions have been implicated in many diseases such as cancer and atherosclerosis. As increasing attention is directed toward these oxidized phospholipids (oxPLs), higher throughput methods are needed to examine interactions between oxPLs and scavenger receptors in the immune system.
View Article and Find Full Text PDFCell Chem Biol
September 2025
iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA 92037, USA; Institute of Molecular Biology and Bio
Balanced or biased G protein and arrestin transmembrane signaling by the adenosine 2A receptor (AAR) is related to ligand-induced allosterically triggered variation of structural dynamics in the intracellular half of the transmembrane domain (TMD). F-nuclear magnetic resonance (NMR) of a network of genetically introduced meta-trifluoromethyl-L-phenylalanine (mtfF) probes in the core of the TMD revealed signaling-related structure rearrangements leading from the extracellular orthosteric drug-binding site to the G protein and arrestin contacts on the intracellular surface. The key element in this structural basis of signal transfer is dynamic loss of structural order in the intracellular half of the TMD, as manifested by local polymorphisms and associated rate processes within the molecular architecture determined previously by X-ray crystallography.
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