Video Experimental Relacionado
Updated: Jan 8, 2026
09:07
Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
Published on: June 14, 2020
11.5K
Ciencia básica y patogénesis
Aparna Unnikrishnan1, Dong Hee Chung1, Emily J Connelly1
1University of California San Francisco, San Francisco, CA, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
Resumen
Los investigadores desarrollaron fragmentos de anticuerpos (Fabs) para estudiar la ligasa E3 CHIP, revelando sus estados estructurales y cómo los Fabs modulan su actividad en las tauropatías. Este trabajo ofrece nuevas dianas terapéuticas para la enfermedad de Alzheimer y trastornos relacionados.
Área de la Ciencia:
- Bioquímica
- Biología Estructural
- Neurociencia
Sus antecedentes:
- La ligasa E3 CHIP interactúa con tau, regulando su recambio y agregación en la enfermedad de Alzheimer y las tauropatías.
- El papel de CHIP en la depuración de tau presenta un objetivo terapéutico, pero su base estructural es desconocida.
- El desarrollo de fragmentos de anticuerpos (Fabs) que se unen a antígenos puede ayudar en estudios estructurales y explorar el potencial terapéutico.
Objetivo del estudio:
- Caracterizar estructural y funcionalmente la ligasa E3 CHIP utilizando nuevos fragmentos de anticuerpos (Fabs) que se unen a antígenos.
- Elucidar la base estructural de la actividad de CHIP y su modulación para la intervención terapéutica en tauropatías.
Principales métodos:
- Se desarrollaron y seleccionaron Fabs recombinantes utilizando ensayos de bio-panning y BLI.
- Se utilizó crio-EM para determinar estructuras de alta resolución de CHIP en complejo con Fabs.
- Se utilizaron ensayos funcionales (ubiquitinación, unión a E2, fibrilación de tau) para evaluar los efectos de Fab en la actividad de CHIP.
Principales resultados:
- La crio-EM reveló tres estados conformacionales distintos de CHIP (dímeros asimétricos, intermedios y simétricos) en solución.
- La unión de Fab moduló la actividad de la ligasa E3 de CHIP y la supresión de la agregación de tau.
- Se identificaron Fabs específicos (2F1, H1, 2D2) con mecanismos distintos de inhibición de CHIP y modulación de la interacción con tau.
Conclusiones:
- El cribado de Fab dilucidó potentes mecanismos de modulación funcional de CHIP.
- Las estructuras de CHIP-Fab proporcionan información sobre la depuración de tau impulsada por CHIP.
- Se identificaron sitios diana terapéuticos únicos en CHIP para el posible desarrollo de fármacos.
Videos de Conceptos Relacionados
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