Related Experiment Video
Updated: Jul 25, 2025
10:41
Why Quantification Matters: Characterization of Phenotypes at the Drosophila Larval Neuromuscular Junction
Published on: May 12, 2016
8.2K
Mutant VAPB: Culprit or Innocent Bystander of Amyotrophic Lateral Sclerosis?
Nica Borgese1, Francesca Navone1, Nobuyuki Nukina2
1CNR Institute of Neuroscience, Vedano al Lambro (MB), Italy.
Contact (Thousand Oaks (Ventura County, Calif.))
|June 27, 2023
Summary
A rare Amyotrophic Lateral Sclerosis (ALS) mutation (p.P56S) in the VAPB gene may cause disease not through toxic effects, but by insufficient levels of functional VAPB protein in motor neurons.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- A mutation in the VAPB gene (p.P56S) causes a rare familial form of Amyotrophic Lateral Sclerosis (ALS).
- VAP proteins are crucial for membrane contact sites between the ER and other organelles.
Purpose of the Study:
- To investigate the mechanistic basis of p.P56S-VAPB in familial ALS.
- To determine whether toxic gain-of-function or insufficient protein levels drive the disease.
Main Methods:
- Literature review of cellular and animal models.
- Analysis of VAPB gene function and protein interactions.
Main Results:
- The p.P56S-VAPB mutation leads to an aggregation-prone, non-functional, and unstable protein.
- Disease pathology is linked to insufficient levels of the wild-type VAPB allele product, not toxic effects.
Conclusions:
- Insufficient VAPB protein levels, rather than toxic gain-of-function, appear to be the primary driver of p.P56S familial ALS.
- Further research distinguishing VAP paralogue roles may clarify ALS pathogenesis.
Related Concept Videos
03:03Amyloid Fibrils
9.6K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.6K
01:23Cystic Fibrosis: Pathogenesis
298
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,...
298