Astrocyte study reveals deleterious changes in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a rapidly progressive neurodegenerative disease that means patients lose strength, speech, and ultimately the ability to breathe

In healthy conditions, astrocytes help protect and nurture surrounding motor neurons

Toxic astroglial changes in amyotrophic lateral sclerosis

In their first paper, published in the journal Genome Research in December, the researchers analyzed all existing public datasets of astrocytes from ALS patients, covering both human and mouse models

ALS astrocytes were also found to lose important protective functions, especially the ability to absorb a substance called glutamate

Oliver Ziff, head of research and clinical investigator in the Human Stem Cell and Neurodegeneration Laboratory at the Crick, said: "Our work shows that treatments for ALS will require reducing or reversing these damaging changes in astrocytes

Innate and multiple deleterious changes in astrocytes in amyotrophic lateral sclerosis (ALS)

In a second study, published today (January 19) in the journal Brain, the researchers found that astrocytes with different genetic mutations that cause ALS also have different underlying molecular patterns

As part of the study, the team examined the effects on astrocytes of different mutations, which are known to cause amyotrophic lateral sclerosis

The nature of these changes depended on the specific mutations present, suggesting that astrocytes in ALS may differ between patients

However, they also showed that some of these changes are clustered together, which may explain why, in disease, astrocytes have similar characteristics and fail to protect motor neurons from degeneration and increased inflammation, which can lead to disease

Study leader Doaa Taha, co-first author of the first paper and PhD student in the Human Stem Cells and Neurodegeneration Laboratory at UCL Crick, said: "Astrocyte transformation between ALS mutations The nature and diversity were not known at the time

Ben Clark, co-first author of both papers and a postdoc in the Human Stem Cell and Neurodegeneration Laboratory, said: "We are now trying to understand the biology of the different molecular patterns we've observed, and how they are How fusion

growth model

While many studies of ALS rely on proven postmortem samples, these studies involve the extraction of living cells from patients

"Our growing understanding of early-stage disease biology is that we find new ways to treat ALS," said Ricky at the time, Crick's Human Stem Cell and Neurodegeneration Laboratory, consultant in Neurology and Neurology at the National Hospital Surgeons and Neuroscientists at the Queen Square Motor Neurone Disease Centre, University of London

Journal References :

1. Doaa M Taha, Benjamin E Clarke, Claire E Hall, Giulia E Tyzack, Oliver J Ziff, Linda Greensmith, Bernadett Kalmar, Mhoriam Ahmed, Aftab Alam, Eric P Thelin, Nuria Marco Garcia, Adel Helmy, Christopher R Sibley, Rickie Patani.

   
   

2. Oliver J.