Protein interaction networks in neurodegenerative diseases: From physiological function to aggregation

Area of Science:

• Neurobiology
• Molecular Biology
• Proteomics

Background:

• Protein inclusions are hallmarks of neurodegenerative diseases, often linked to aging, genetics, and environmental factors.
• While disease mechanisms are complex, protein-protein interactions significantly regulate the aggregation of disease-associated proteins.

Purpose of the Study:

• To review current knowledge on protein-protein interactions involving key aggregation-prone proteins in Alzheimer's, Parkinson's, Huntington's, and ALS.
• To provide an overview of protein interaction networks driving or mitigating inclusion formation.

Main Methods:

• Literature review of proteomic studies and research on protein aggregation in neurodegenerative diseases.
• Analysis of protein-protein interaction networks associated with key aggregation-prone proteins.

Main Results:

• Protein interactions with molecular chaperones and proteolytic systems are crucial for managing misfolded proteins.
• Sequestration of functional proteins in inclusions leads to loss of function.
• Altered protein interactions due to mutations or misfolding can disrupt cellular processes and organelles.

Conclusions:

• Protein-protein interactions are central to the pathogenesis and progression of major neurodegenerative diseases.
• Understanding these networks offers potential therapeutic targets for preventing or clearing protein inclusions.