# APP-C31 pathology as a target in neurodegenerative diseases

## TL;DR

This paper explores APP-C31's role in neurodegenerative diseases and suggests it could be a key target for new therapies.

## Contribution

The paper proposes a novel hypothesis that APP-C31 is a central executioner linking upstream stressors to downstream neurodegeneration.

## Key findings

- APP-C31 is suggested to act as a multi-functional signaling hub driving pathogenic pathways.
- Diverse upstream stressors initiate the cascade leading to APP-C31 generation.
- APP-C31 may amplify molecular damage into macroscopic neurodegeneration.

## Abstract

Neurodegenerative diseases (Alzheimer’s disease, Parkinson's disease, Huntington’s disease, etc.) are caused by the progressive loss of neurons, which affects many people worldwide. Therefore, many efforts have focused on neurodegenerative disease mechanisms and therapeutic strategies. Moreover, amyloid precursor proteins and their cleaving products, including APP-C31, may play important roles in neurodegeneration. This review provides a comprehensive introduction to the structure, neurotoxicity, regulatory mechanism, and relevance of APP-C31 to clinical diseases and its therapeutic potential as a drug target. This work will bridge the gap in our understanding of the function of APP-C31, which provides an experimental basis for neurodegenerative disease therapeutics. Meanwhile, a hypothesis is postulated that the APP-C31 functions not merely as a byproduct of caspase cleavage, but as the critical "central executioner" bridging upstream triggers and downstream neurodegeneration. Diverse upstream stressors, initiate the cascade to generate APP-C31. Once generated, C31 acts as a multi-functional signalling hub driving four distinct pathogenic pathways. Consequently, APP-C31 is hypothesized to be the essential mediator that amplifies these molecular damages into macroscopic failures.