Racemization in Post-Translational Modifications Relevance to Protein Aging, Aggregation and Neurodegeneration: Tip...

Area of Science:

• Biochemistry
• Neuroscience
• Molecular Biology

Background:

• Homochirality of DNA and amino acids is fundamental to life.
• Racemization (loss of chirality) is linked to aging, disease, and neurodegeneration.
• Protein folding, aggregation, and function are influenced by amino acid chirality.

Purpose of the Study:

• To explore the role of amino acid racemization in protein structure, function, and neurodegenerative diseases.
• To investigate the link between altered homochirality and cognitive function.
• To propose racemization as a critical factor in protein misfolding and aggregation.

Main Methods:

• Thermodynamic analysis of homochiral and racemized states.
• Examination of spontaneous and enzymatic racemization mechanisms.
• Review of literature linking racemization to protein conformational changes and disease.

Main Results:

• Racemization leads to a loss of homochirality, resulting in conformational phase transitions in proteins.
• Both spontaneous and enzymatic racemization occur via thermal activation or quantum tunneling.
• Age-dependent racemization affects key proteins implicated in neurodegenerative disorders (e.g., APP, TAU, PrP).

Conclusions:

• Racemization is a critical factor influencing protein conformation, potentially inducing misfolding, aggregation, and dysfunction.
• The balance between homochirality and racemization is crucial for maintaining cognitive function.
• Racemization offers a new perspective on the pathogenesis of neurodegenerative diseases and potential therapeutic targets.