scholarly journals ALS-associated genes in SCA2 mouse spinal cord transcriptomes

2020 ◽  
Vol 29 (10) ◽  
pp. 1658-1672 ◽  
Author(s):  
Daniel R Scoles ◽  
Warunee Dansithong ◽  
Lance T Pflieger ◽  
Sharan Paul ◽  
Mandi Gandelman ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Innate Immunity ◽  
Motor Neuron ◽  
Complement System ◽  
Fatty Acid Biosynthesis ◽  
Cholesterol Biosynthesis ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Als Patients ◽  
The Complement System

Abstract The spinocerebellar ataxia type 2 (SCA2) gene ATXN2 has a prominent role in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS). In addition to cerebellar ataxia, motor neuron disease is often seen in SCA2, and ATXN2 CAG repeat expansions in the long normal range increase ALS risk. Also, lowering ATXN2 expression in TDP-43 ALS mice prolongs their survival. Here we investigated the ATXN2 relationship with motor neuron dysfunction in vivo by comparing spinal cord (SC) transcriptomes reported from TDP-43 and SOD1 ALS mice and ALS patients with those from SCA2 mice. SC transcriptomes were determined using an SCA2 bacterial artificial chromosome mouse model expressing polyglutamine expanded ATXN2. SCA2 cerebellar transcriptomes were also determined, and we also investigated the modification of gene expression following treatment of SCA2 mice with an antisense oligonucleotide (ASO) lowering ATXN2 expression. Differentially expressed genes (DEGs) defined three interconnected pathways (innate immunity, fatty acid biosynthesis and cholesterol biosynthesis) in separate modules identified by weighted gene co-expression network analysis. Other key pathways included the complement system and lysosome/phagosome pathways. Of all DEGs in SC, 12.6% were also dysregulated in the cerebellum. Treatment of mice with an ATXN2 ASO also modified innate immunity, the complement system and lysosome/phagosome pathways. This study provides new insights into the underlying molecular basis of SCA2 SC phenotypes and demonstrates annotated pathways shared with TDP-43 and SOD1 ALS mice and ALS patients. It also emphasizes the importance of ATXN2 in motor neuron degeneration and confirms ATXN2 as a therapeutic target.

The Role of the Complement System in Innate Immunity

2005 ◽  
Vol 33 (2) ◽  
pp. 103-112 ◽  
Author(s):  
Horea Rus ◽  
Cornelia Cudrici ◽  
Florin Niculescu
Keyword(s):  
Innate Immunity ◽  
Complement System ◽  
The Complement System

scholarly journals Role of Complement in Multiorgan Failure

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Daniel Rittirsch ◽  
Heinz Redl ◽  
Markus Huber-Lang
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Inflammatory Response ◽  
Complement System ◽  
Multiorgan Failure ◽  
Severe Trauma ◽  
Organ Systems ◽  
Activation Products ◽  
The Complement System

Multiorgan failure (MOF) represents the leading cause of death in patients with sepsis and systemic inflammatory response syndrome (SIRS) following severe trauma. The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed.

scholarly journals The many roles of C1q

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Mark Noble ◽  
Christoph Pröschel
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Complement System ◽  
Complement Cascade ◽  
Cord Injury ◽  
The Many ◽  
The Complement System

The ability of a well-known component of the complement cascade to bind to a variety of receptors has implications for signaling biology, spinal cord injury and, possibly, the evolution of the complement system.

scholarly journals Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients

2021 ◽  
Vol 10 (22) ◽  
pp. 5251
Author(s):  
Anna Sobuś ◽  
Bartłomiej Baumert ◽  
Monika Gołąb-Janowska ◽  
Piotr Kulig ◽  
Edyta Paczkowska ◽  
...  
Keyword(s):  
Immune System ◽  
Cell Therapy ◽  
Complement System ◽  
Autologous Bone Marrow ◽  
Medical Intervention ◽  
Complement Components ◽  
Inflammatory Reactions ◽  
Sporadic Als ◽  
Als Patients ◽  
The Complement System

ALS remains a fatal, neurodegenerative motor neuron disease. Numerous studies seem to confirm that innate immune system is involved in the pathophysiology of ALS. Hence, the assessment of the complement system and attempts to modify its activity remain the target of medical intervention in ALS. In the present study, three intrathecal administrations of autologous bone marrow-derived lineage-negative (Lin–) cells were performed every 6 weeks in 20 sporadic ALS patients. The concentrations of various complement components in the cerebrospinal fluid and plasma at different time points after cell injection were quantified using a Luminex multiplex. The results of the complement system were correlated with the level of leukocytes, neutrophils, lymphocytes, fibrinogen and CRP in the peripheral blood and the functional status of ALS patients using Norris and ALS-FRSr scales. The study showed a statistically significant decrease in plasma C3b concentration in all 7th days after cell application. In parallel, a peak decrease in neutrophil count and CRP level was observed on days 5–7, with a simultaneous maximum clinical improvement on days 7–28 of each Lin– cell administration. Adjuvant Lin– cell therapy appears to have the silencing potential on the complement-mediated immune system and thus suppress pro-inflammatory reactions responsible for neurodegeneration. However, further in-depth studies are necessary to address this issue.

scholarly journals Modulation of the Complement System by Neoplastic Disease of the Central Nervous System

2021 ◽  
Vol 12 ◽  
Author(s):  
Steven K. Yarmoska ◽  
Ali M. Alawieh ◽  
Stephen Tomlinson ◽  
Kimberly B. Hoang
Keyword(s):  
Central Nervous System ◽  
Innate Immunity ◽  
Nervous System ◽  
Adaptive Immunity ◽  
Complement System ◽  
Neoplastic Disease ◽  
Innate And Adaptive Immunity ◽  
Neoplastic Diseases ◽  
The Central Nervous System ◽  
The Complement System

The complement system is a highly conserved component of innate immunity that is involved in recognizing and responding to pathogens. The system serves as a bridge between innate and adaptive immunity, and modulation of the complement system can affect the entire host immune response to a foreign insult. Neoplastic diseases have been shown to engage the complement system in order to evade the immune system, gain a selective growth advantage, and co-opt the surrounding environment for tumor proliferation. Historically, the central nervous system has been considered to be an immune-privileged environment, but it is now clear that there are active roles for both innate and adaptive immunity within the central nervous system. Much of the research on the role of immunological modulation of neoplastic disease within the central nervous system has focused on adaptive immunity, even though innate immunity still plays a critical role in the natural history of central nervous system neoplasms. Here, we review the modulation of the complement system by a variety of neoplastic diseases of the central nervous system. We also discuss gaps in the current body of knowledge and comment on future directions for investigation.

scholarly journals Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy

2005 ◽  
Vol 14 (14) ◽  
pp. 1991-2002 ◽  
Author(s):  
Yvette P. Conley ◽  
Anbupalam Thalamuthu ◽  
Johanna Jakobsdottir ◽  
Daniel E. Weeks ◽  
Tammy Mah ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Candidate Gene ◽  
Complement System ◽  
Fatty Acid Biosynthesis ◽  
Gene Analysis ◽  
Acid Biosynthesis ◽  
Candidate Gene Analysis ◽  
Age Related ◽  
The Complement System

scholarly journals Congenital immunity in patients with essential arterial hypertension and effectiveness of antihypertensive pharmacotherapy

2020 ◽  
pp. 27-33
Author(s):  
Vadim P. Mikhin ◽  
Evgenia V. Gavrilyuk ◽  
Irina V. Evsegneeva
Keyword(s):  
Blood Pressure ◽  
Innate Immunity ◽  
Arterial Hypertension ◽  
Antihypertensive Therapy ◽  
Complement System ◽  
Control Group ◽  
Target Values ◽  
Essential Arterial Hypertension ◽  
Group 2 ◽  
The Complement System

The purpose of the study was to assess the parameters of innate immunity in patients with essential arterial hypertension and to establish a relationship with the effectiveness of antihypertensive pharmacotherapy. Materials and methods. The study included 48 patients with essential arterial hypertension stage II, arterial hypertension 2 degree and hypertrophy of the left ventricular myocardium, which were divided into 2 groups: the first group (25 patients) - these are patients whose blood pressure reached the target values, and the second group (23 patients) are patients whose blood pressure did not reach the target values against the background of antihypertensive therapy (perindopril - 5 mg/day and amlodipine - 5 mg/day) (group 2). Indicators of 18 healthy donors were used as a comparison group (control group). Results. In patients with essential arterial hypertension of group 1, compared with the control group, the concentration of IL-1α, IL-6, IL-8, IL-10, IL-1 receptor antagonist, IL-2, C4- and C5a-components of the complement system and factor H is significantly higher and the level of C3 is lower-component of the complement system. In patients with essential arterial hypertension of group 2, more pronounced changes in the cytokine link of the immunity and the complement system were established before the start of antihypertensive therapy. After the antihypertensive therapy in patients with essential arterial hypertension of the 1st group in the blood plasma, the concentration of TNF, IL-1α, IL-8, IL-10, IL-1 receptor antagonist significantly decreased, but not to the values of the control group, and in patients of the 2nd group, the effectiveness of antihypertensive therapy in correcting parameters innate immunity was found to be less effective. Conclusion. Revealing the participation of innate immunity indicators in the formation of arterial hypertension opens up new possibilities for the pathogenetic therapy of this disease and developing measures to prevent or level the damage to target organs.

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