Scientists have long focused on amyloid beta buildup as the main cause of Alzheimer’s disease, but a new study suggests that stalled protein-cutting processes in the brain may be the real culprit.
Researchers found that mutations in the PSEN1 gene disrupt how the γ-secretase enzyme trims amyloid precursor protein (APP), leading to the accumulation of harmful intermediates. This discovery shifts the spotlight from amyloid beta to the enzyme’s failure to properly process APP, opening new doors for treatment strategies that could restore this disrupted process.
According to the study, published in eLife, Alzheimer’s disease is likely caused by stalled protein processing in the brain. The researchers explored how mutations in the presenilin-1 (PSEN1) gene interfere with the processing of amyloid precursor protein (APP). Normally, APP is broken down into amyloid beta (Aβ) protein, which can accumulate in the brains of people with Alzheimer’s.
The study provides strong evidence and detailed analysis supporting this connection, and its findings could help in the development of new Alzheimer’s treatments. By focusing on familial Alzheimer’s disease, the researchers have simplified the identification of pathogenic mechanisms, opening the door to developing new treatments.
The team discovered that mutations in the PSEN1 gene lead to stalled protein-cutting processes, which increase the stability of enzyme-substrate complexes. This result makes sense alongside initial proteolysis analysis, which suggests that the proteolytic process had stalled.
Implications for future Alzheimer’s treatments include the proposal of γ-secretase activators that can rescue stalled proteolysis and complement treatments targeting other Alzheimer’s-associated pathways.
Source: https://scitechdaily.com/breakthrough-study-reveals-how-protein-glitches-may-be-driving-alzheimers