Autophagy role in axonal integrity in the brain

Autophagy role in axonal integrity in the brain

Scientists from have found out that autophagy - the process of cellular self-recycling, or waste clearance - is dispensable for the survival of the neurons in mice. The new findings suggest that autophagy in fact also fulfils a different important function: The proteins classically associated with waste clearance in cells regulate the speed of intracellular transport. This transport is achieved by microscopic hollow tubes, so-called microtubules (MT).

Autophagy cleans the cells by breaking down and removing the damaged proteins and organelles, cell areas with a specific function. It is hardly surprising that this process is particularly important for long-lived cells such as neurons, since neurons are no longer capable of cell division ('post-mitotic') and are therefore particularly vulnerable to accumulating unfavorable proteins and damaged organelles. In their new study published in Nature Communications, the scientists show that neurons in the mouse brain do not need autophagy to survive. Instead, these specialized cells use autophagy proteins to regulate the MT-dependent transport of molecules crucial for learning and memory.

The authors report on a regulation of MT dynamics by AuTophaGy(ATG)-related proteins, which previously have been linked to the autophagy pathway. They find that ATG proteins required for LC3 lipid conjugation are dispensable for survival of excitatory neurons and instead regulate MT stability via controlling the abundance of the MT-binding protein CLASP2. This function of ATGs is independent of their role in autophagy and requires the active zone protein ELKS1. 

The fact that autophagy is crucial for the well-being of the brain is supported by scientific discoveries made over the last decade. Many studies have identified defective autophagy as one of the pathological causes of neurodegenerative diseases, including Alzheimer's (AD), Parkinson's and Huntington's disease. In this context, the novel function of autophagy the scientists discovered suggests that the therapeutic modulations of autophagy activity in patients might not only promote the waste clearance in the brain, but also alter the cognitive abilities by changing the efficiency of the intracellular transportation system.