In vitro studies suggest that insulin-like growth factor (IGF)-I is a mitogen for microglia/macrophages. The actions of IGF-I are mediated by IGF-I receptors and modulated by IGF binding proteins (IGFBPs). The aim of this study was to investigate IGF-I receptors and IGFBPs in human microglia in normal brain white matter and active lesions of multiple sclerosis, which contain activated microglia/macrophages. Methods used were immunohistochemistry and confocal laser microscopy. IGF-I receptors were demonstrated in both resting and activated microglia. In resting conditions, microglia displayed no immunoreactivity for any of the six IGFBPs, whereas activated microglia/macrophages were immunoreactive for IGFBP-2 only. Our data suggest an important function for IGFBP-2 in IGF-I actions in activated microglia/macrophages in human brain.
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http://dx.doi.org/10.1016/j.neulet.2004.01.039 | DOI Listing |
Protein Eng Des Sel
January 2025
Pfizer Rare Disease Research Unit, 610 Main Street, Cambridge, MA 02139, United States.
Pompe disease is a tissue glycogen disorder caused by genetic insufficiency of the GAA enzyme. GAA enzyme replacement therapies for Pompe disease have been limited by poor lysosomal trafficking of the recombinant GAA molecule through the native mannose-6-phosphate-mediated pathway. Here, we describe the successful rational engineering of a chimeric GAA enzyme that utilizes the binding affinity of a modified IGF-II moiety to its native receptor to bypass the mannose-6-phosphate-mediated lysosomal trafficking pathway, conferring a significant increase in cellular uptake of the GAA enzyme.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
The pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is generally attributed to vascular smooth muscle cell (VSMC) pathologies. However, the role of immune cell-mediated inflammation remains elusive. Single-cell RNA sequencing identified a subset of CX3CR1+ macrophages mainly located in the intima in the aortic roots and ascending aortas of Fbn1C1041G/+ mice, further validated in MFS patients.
View Article and Find Full Text PDFTransl Psychiatry
January 2025
Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Anxiety disorder, a prevalent mental health issue, is one of the leading causes of disability worldwide. Damage to the blood-brain barrier (BBB) is implicated in anxiety, but its regulatory mechanisms remain unclear. Herein, we show that adrenomedullin 2 (ADM2), a novel angiogenic growth factor, alleviates autistic and anxiety-like behaviors in mice.
View Article and Find Full Text PDFJ Neuroophthalmol
December 2024
Experimental and Clinical Research Center (FCO, HGZ, SM, CB, ESA, CC, FP, AUB), Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; NeuroCure Clinical Research Center (FCO, HGZ, SM, CB, ESA, CC, FP, AUB), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Neurology (AJG), University of California San Francisco, San Francisco, California; Neurology (RM, ACC), Multiple Sclerosis, Myelin Disorders and Neuroinflammation Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, France; Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (ACC), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; Experimental Neurophysiology Unit (LL, MP, M. Radaelli), Institute of Experimental Neurology (INSPE) Scientific Institute, Hospital San Raffaele and University Vita-Salute San Raffaele, Milan, Italy; Hospital Clinic of Barcelona-Institut d'Investigacions (PV, BS-D, EHM-L), Biomèdiques August Pi Sunyer, (IDIBAPS), Barcelona, Spain; CIEM MS Research Center (MAL-P, MAF), University of Minas Gerais, Medical School, Belo Horizonte, Brazil; Department of Neurology (OA, M. Ringelstein, PA), Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Department of Neurology (M. Ringelstein), Centre for Neurology and Neuropsychiatry, LVR Klinikum, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Department of Medicine (MRY), Harbor-University of California at Los Angeles (UCLA) Medical Center, and Lundquist Institute for Biomedical Innovation, Torrance, California; Department of Medicine (MRY), David Geffen School of Medicine at UCLA, Los Angeles, California; Departments of Ophthalmology and Visual Sciences (TJS), Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Michigan; Division of Metabolism, Endocrine and Diabetes (TJS, LC), Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan; Department of Neurology (FP), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; and Department of Neurology (AUB), University of California, Irvine, California.
Int J Mol Sci
January 2025
Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain.
Matrix metalloproteinases (MMPs) are M2 macrophage markers that are modulated by inflammation. A disintegrin and metalloproteinases (ADAMS) and those with thrombospondin motifs (ADAMTS) regulate the shedding of membrane-bound proteins, growth factors, cytokines, ligands, and receptors; MMPs, ADAMS, and ADAMTS may be regulated by tissue inhibitors of metalloproteinases (TIMPs). This study aimed to determine whether these interacting proteins were dysregulated in PCOS.
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