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Synthesis and biological evaluation of novel pyrrolo[2,3-b]pyridine derivatives as potent GSK-3β inhibitors for treating Alzheimer's disease.
Eur J Med Chem
January 2025
Medical Research Center, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China. Electronic address:
The development of potent glycogen synthase kinase-3β (GSK-3β) inhibitor has been increasingly recognized as the candidate treatment against the multifactorial pathogenic mechanism of Alzheimer's disease (AD). This study prepared various new pyrrolo[2,3-b]pyridine derivatives, evaluated the anti-AD activities and detected the security based on the structure-guided rational design. Our results indicated that many pyrrolo[2,3-b]pyridine derivatives had strong GSK-3β inhibitory activities, particularly compounds 41, 46 and 54, with the half maximal inhibitory concentrations (IC) of 0.
View Article and Find Full Text PDFNeonatal systemic gene therapy restores cardiorespiratory function in a rat model of Pompe disease.
bioRxiv
December 2024
Department of Pediatrics, University of Florida, Gainesville, FL.
Absence of functional acid-α-glucosidase (GAA) leads to early-onset Pompe disease with cardiorespiratory and neuromuscular failure. A novel Pompe rat model ( ) was used to test the hypothesis that neonatal gene therapy with adeno-associated virus serotype 9 (AAV9) restores cardiorespiratory neuromuscular function across the lifespan. Temporal vein administration of AAV9-DES-GAA or sham (saline) injection was done on post-natal day 1; rats were studied at 6-12 months old.
View Article and Find Full Text PDF[Electroacupuncture reduces neuronal apoptosis in rats with spinal cord injury by regulating GSK-3β expression and its phosphorylation].
Zhen Ci Yan Jiu
November 2024
College of Acupuncture-moxibustion and Massage, Beijing University of Chinese Medicine, Beijing 102488, China.
Objectives: To observe the effect of electroacupuncture (EA) stimulation of "Dazhui"(GV14) and "Mingmen" (GV4) of the Governor Vessel (GV) on the apoptosis of neurons in rats with spinal cord injury (SCI) by regulating the expression of glycogen synthase kinase-3β (GSK-3β) protein and its phosphorylation level, so as to reveal partial mechanism for the treatment of SCI with EA of GV.
Methods: A total of 45 male SD rats were randomly divided into sham-operation, model and EA groups, 15 rats in each group. The SCI model was established by using the modified Allen's percussion device.
[Drug developmental strategies based on functional analysis of pain-regulating molecules in astrocytes under chronic pain].
Nihon Yakurigaku Zasshi
November 2024
Department of Pharmacology, Hiroshima University Graduate School of Biomedical and Health Sciences.
Spinal cord astrocytes are activated in chronic pain models, especially under conditions of prolonged pain. Hence, targeting spinal cord astrocytes for the development of useful analgesics has attracted much attention. In the CNS, connexin43 (Cx43), a membrane protein expressed and functioning exclusively in astrocytes, is well known to be involved in intercellular signaling as a component of gap junction, but also interacts with intracellular molecules via its characteristically long C-terminal region, thereby affecting cellular function.
View Article and Find Full Text PDFUnusual presentation of PYGM gene mutation as late-onset McArdle disease with camptocormia: a case report.
J Med Case Rep
October 2024
Department of Neurology, Carl Von Ossietzky University Oldenburg, Oldenburg, Germany.
Background: Glycogen storage disease type 5 (McArdle disease) leads to a deficiency in the activity of myophosphorylase resulting in an impaired glucose utilization. The disease can be caused by a variety of mutations in the PYGM gene, and its typical clinical manifestation is muscles weakness within the first three decades of life.
Case Presentation: In this case report we present the diagnostic work-up of a physically active 78-year-old Caucasian patient suffering from a 2-year history of progressive camptocormia including clinical, radiologic, histological, and genetic tests.
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