# Coenzyme A in Brain Biology and Neurodegeneration

## TL;DR

This paper reviews the role of Coenzyme A in brain function and how its deficiency can lead to neurodegeneration, suggesting new ways to treat these diseases.

## Contribution

The paper highlights recent advances in understanding CoA's role in neuronal metabolism and redox regulation, particularly through protein CoAlation.

## Key findings

- Disruptions in CoA biosynthesis lead to neurodegeneration, emphasizing CoA's importance in neuronal viability.
- Protein CoAlation is identified as a novel mechanism for antioxidant function and redox regulation.
- New analytical tools may help develop better diagnostics and therapies for neurodegenerative diseases.

## Abstract

Coenzyme A (CoA) biology has been extensively studied in health and disease due to the central role of CoA in numerous metabolic and signalling processes. CoA is essential for all living organisms, and its biosynthesis and homeostasis are tightly regulated by nutrient availability, mitogenic stimuli, and stress signals. Disruptions in CoA biosynthesis, caused by inborn mutations in genes encoding enzymes of the CoA biosynthetic pathway (such as PANK2 and CoASy), lead to neurodegeneration, indicating the critical role of CoA/CoA thioesters in the function and viability of neuronal cells. The molecular mechanisms linking CoA deficiency to neurodegeneration remain unknown, but recent studies have highlighted the involvement of disrupted metabolism and redox homeostasis. The antioxidant function of CoA, mediated by protein CoAlation, has recently emerged as a novel and important mechanism of redox regulation. This review highlights well-established principles of CoA in neuronal metabolism and summarises recent advances in our understanding of its role in adaptive responses to oxidative and metabolic stress. The identification of enzymes involved in the CoAlation/deCoAlation cycle, together with the development of novel analytical tools and methodologies, may provide new insights into the discovery of more effective diagnostic and therapeutic approaches for targeting neurodegenerative diseases.