SIRPα deficiency accelerates the pathologic process in models of Parkinson disease

Abstract

Microglia‐mediated neuroinflammation is a crucial pathophysiological contributor to several aging‐related neurodegenerative disorders, including Parkinson's disease (PD). During the process of aging or stress, microglia undergoes several transcriptional and morphological changes that contribute to aberrant immunological responses, which is known as priming. Key molecules involved in the process, however, are not clearly defined. In the present study, we have demonstrated that level of microglial signal regulatory protein α (SIRPα) decreased during aging or inflammatory challenge. Functional studies suggested that downregulation of SIRPα released the brake of inflammatory response in microglia, revealing an inhibitory effect of SIRPα in microglial activation. Furthermore, we assessed the impact of SIRPα downregulation in PD pathogenesis using both cell culture and animal models. Our results showed that SIRPα deficiency resulted in abnormal inflammatory response and phagocytic activity of microglia, which in turn, further accelerated degeneration of dopaminergic neurons in 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine or lipopolysaccharides mice models. These results collectively demonstrate that dysregulation of SIRPα signaling in microglia during aging plays a critical role in the pathogenesis of age‐related neurological disorders such as PD.

Delivering Antisense Oligonucleotides across the Blood‐Brain Barrier by Tumor Cell‐Derived Small Apoptotic Bodies

“…Encouraged by the in vitro anti‐inflammatory effects, we further tested whether sCABs were efficacious in the treatment of PD in a mouse model induced by intra‐substantia nigra pars compacta (SNc) LPS injection. [ 39–40 ] The prevention test was conducted as shown in Figure a. Briefly, mice were given sCABs (3.5 µg ASO delivered by 2.7 × 10 9 sCABs per injection) 4 times iv .…”

“…[48] The primary astrocytes and microglial cells were obtained from the gray matter of neonatal mice. [30,40] The astrocytes were then analyzed with GFAP and the microglial cells with IBA-1, as well as a FITC-CD11b antibody (101205, eBioscience, USA) by flow cytometry. b. End3 cells were first seeded on the apical side of the permeable filter at 5 × 10 4 cells cm −2 and astrocytes in the bottom chamber.…”

Podocytes present antigen to activate specific T cell immune responses in inflammatory renal disease

“…Mice were deeply anesthetized and perfused with HBSS, the kidneys were removed and immediately fixed in 4% paraformaldehyde. Tissues were embedded in paraffin wax for immunohistochemical staining, as published previously [18]. Tissue sections were incubated with 10% horse serum and 0.3% Triton-X100 in PBS at room temperature for 45 min, and then anti-CD8 antibody (R&D Systems, Minnesota, USA, MAB116, 1:100) overnight at 4 C. After incubation with a secondary peroxidase-conjugated antibody, the signal was generated using DAB (Vector Laboratories, California, USA, SK-4100) and the images were captured by microscopy (Olympus BX53).…”

Facet‐Dependent Biodegradable Mn3O4 Nanoparticles for Ameliorating Parkinson's Disease

“…Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in the world and has been estimated to affect 10 million people worldwide. [1,2] The key pathological changes of Parkinson's disease are the degeneration and death of dopaminergic neurons; this results in the loss of dopaminergic neurons in the striatum. [3][4][5] Scavenging reactive oxygen species (ROS) is an effective strategy to alleviate the symptoms of PD.…”