title: S100B Inhibitor Pentamidine Attenuates Reactive Gliosis and Reduces Neuronal Loss in a Mouse Model of Alzheimer's Disease.
abstract: Among the different signaling molecules released during reactive gliosis occurring in Alzheimer's disease (AD), the astrocyte-derived S100B protein plays a key role in neuroinflammation, one of the hallmarks of the disease. The use of pharmacological tools targeting S100B may be crucial to embank its effects and some of the pathological features of AD. The antiprotozoal drug pentamidine is a good candidate since it directly blocks S100B activity by inhibiting its interaction with the tumor suppressor p53. We used a mouse model of amyloid beta- (Aβ-) induced AD, which is characterized by reactive gliosis and neuroinflammation in the brain, and we evaluated the effect of pentamidine on the main S100B-mediated events. Pentamidine caused the reduction of glial fibrillary acidic protein, S100B, and RAGE protein expression, which are signs of reactive gliosis, and induced p53 expression in astrocytes. Pentamidine also reduced the expression of proinflammatory mediators and markers, thus reducing neuroinflammation in AD brain. In parallel, we observed a significant neuroprotection exerted by pentamidine on CA1 pyramidal neurons. We demonstrated that pentamidine inhibits Aβ-induced gliosis and neuroinflammation in an animal model of AD, thus playing a role in slowing down the course of the disease.
authors: Laboratory for Enteric NeuroScience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, 3000 Leuven, Belgium.
authors: Carla
authors: C
authors: Cirillo
authors: Laboratory for Enteric NeuroScience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, 3000 Leuven, Belgium ; Department of Physiology and Pharmacology "Vittorio Erspamer", La Sapienza University of Rome, 00185 Rome, Italy.
authors: Elena
authors: E
authors: Capoccia
authors: Department of Pharmacy, Federico II University of Naples, 80131 Naples, Italy.
authors: Teresa
authors: T
authors: Iuvone
authors: Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy.
authors: Rosario
authors: R
authors: Cuomo
authors: Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy.
authors: Giovanni
authors: G
authors: Sarnelli
authors: Department of Physiology and Pharmacology "Vittorio Erspamer", La Sapienza University of Rome, 00185 Rome, Italy.
authors: Luca
authors: L
authors: Steardo
authors: Department of Physiology and Pharmacology "Vittorio Erspamer", La Sapienza University of Rome, 00185 Rome, Italy.
authors: Giuseppe
authors: G
authors: Esposito
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003720:Densitometry; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000473:pathology; D007267:Injections; D053583:Interleukin-1beta / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009573:Nitrites / Q000378:metabolism; D010419:Pentamidine / Q000494:pharmacology / Q000627:therapeutic use*; D064568:S100 Calcium Binding Protein beta Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D009573:Nitrites; D064568:S100 Calcium Binding Protein beta Subunit; D016159:Tumor Suppressor Protein p53; D008315:Malondialdehyde; D010419:Pentamidine; D015232:Dinoprostone