Past neuroscience research found a link between iron dysregulation and different neurodegenerative diseases. Moreover, brain regions associated with these diseases are full of iron packed microglia. For example, resident immune cells.
There is enough documented information on the association between iron dysregulation and neurodegenerative diseases. But the mechanism behind iron accumulation affecting the physiology of microglia and neurodegeneration is still unknown.
Hence, a study has recently been carried out by the healthcare company Sanofi. The study aims to fill this literature gap by understanding how microglia respond to iron.
Timothy Hammond, one of the researchers of the study said,
The main aim of the recent work by Hammond and his colleagues was to understand how health and functioning are affected by iron accumulation in microglia.
Moreover, the work has been built on previous studies and the 2012 iron-dependent form of cell death discovered, called ferroptosis. The researchers also hypothesized that iron-laden microglia are prone to ferroptosis, which may play a role in neurodegenerative diseases.
The experiment was conducted by the researchers by growing microglia in a tri-culture system. With the use of a series of genetic and experimental techniques, the researchers showed that microglia response to iron and are also prone to ferroptosis.
Additionally, the team also showed that iron overlead causes a microglial transcriptional state shift, overlapping with the transcriptomic signature, which is seen in brain tissue microglia from deceased patients with PD. Moreover, when the microglia was removed from the tri-culture system, iron neurotoxicity became slow. Suggesting that microglia responds to iron overload and plays a crucial role in neurodegeneration.
In conclusion, this first every study on iron induced neurotoxicity can make way for various new discoveries and development of therapeutic interventions.