Related Experiment Video
Updated: Jan 8, 2026
09:07
Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
Published on: June 14, 2020
11.5K
Basic Science and Pathogenesis
Jack Badman1, Bjorn Bakker1, Rajnish Kumar2
1Karolinska Institutet, Solna, Sweden.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
Summary
Deleting the signal peptidyl peptidase 2b (SPPL2b) gene reduced amyloid-beta pathology and synaptic loss in an Alzheimer's disease (AD) mouse model. This study identified potential SPPL2b inhibitors for AD therapy.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Signal peptidyl peptidase 2b (SPPL2b) is an intramembrane peptidase implicated in Alzheimer's disease (AD) pathophysiology.
- SPPL2b cleaves transmembrane proteins such as APP, influencing amyloid-beta (Aβ) production.
- Previous studies indicated SPPL2b inhibition reduces Aβ42 and Aβ40 production.
Purpose of the Study:
- To explore the therapeutic potential of SPPL2b inhibition in AD.
- To investigate the effects of SPPL2b gene deletion in an AD mouse model.
- To identify potential SPPL2b inhibitory compounds through in silico screening.
Main Methods:
- Generated a novel AD mouse model by crossing AppNL-G-F mice with SPPL2b-deficient mice.
- Analyzed brain samples using western blotting, immunofluorescence, and Golgi staining.
- Screened the Vitas-M commercial library to identify potential SPPL2b inhibitors.
Main Results:
- SPPL2b knockout significantly reduced Aβ plaque deposition and gliosis in AD mice.
- SPPL2b deletion protected against synaptic loss and decreased phospho-tau intensity.
- Identified 100 potential SPPL2b inhibitory compounds.
Conclusions:
- SPPL2b plays a critical role in AD Aβ pathology development.
- SPPL2b is a promising therapeutic target for AD prevention and mitigation.
- Identified compounds are undergoing evaluation for in vitro and in vivo efficacy.
Related Concept Videos
01:20Infection
11.6K
When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
11.6K
01:25Urinary Tract Infection II: Pathophysiology
524
The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
524
01:23Cystic Fibrosis: Pathogenesis
676
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
676
01:29Pneumonia II: Pathophysiology
2.5K
The pathophysiology of pneumonia involves the following steps:
2.5K
01:26Stages of Infection
64.7K
Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
64.7K
01:31Defense Against Bacterial Pathogens
2.6K
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
2.6K