Scientists Reprogram Skin Cells into Aged Neurons to Improve Research on Age-Related Brain Disorders

A team of scientists from Lund University in Sweden has developed a new system that could make research into neurodegenerative disorders less difficult than it has been to date.

skin cells to neurons

HD-iNs (Huntington’s disease-induced neurons) show altered autophagy specifically in neurites. (A) BECN1 expression is reduced in HD-iNs compared to control neurons (Ctrl-iNs), as shown by western blot analysis (10 replicates for controls, 9 for HD-iNs). (B) LC3B-II levels are significantly elevated in HD-iNs, while the LC3B-II/I ratio is lower than in Ctrl-iNs (6 replicates). (C–H) Images and statistical analysis reveal a significant increase in both the number and size of LC3B, p62, and LAMP1 markers in the MAP2+ neurites of HD-iNs compared to controls (6 lines). (I) Post-mortem images from healthy controls and Huntington’s disease patients at various stages show p62 accumulation in neurites, highlighted by a neurofilament-specific antibody. Statistical significance is indicated as ***P < 0.001; **P < 0.01; *P < 0.05, using two-tailed unpaired T-tests. Data are presented as mean ± SEM, with western blot values normalized to Ctrl-iNs and adjusted for actin. Scale bar = 20 µm. Credit: Brain (2021). DOI: 10.1093/brain/awab473

These researchers focused on Huntington’s disease, a neurodegenerative disorder that is particularly challenging to understand. In their study, they succeeded in reprogramming human skin cells into aged neurons to better study the condition.

The team’s findings were recently published in the journal Brain.

A Major Obstacle to Research

One of the key challenges that scientists often face in experimental research is creating accurate models of specific diseases. Overcoming this hurdle would allow researchers to achieve more in their studies and develop more effective treatments.

Huntington’s disease is a prime example of a disorder that has proven difficult to model. The mechanisms underlying the disease remain elusive, partly because of the complexity involved in recreating suitable cellular or animal models, researchers said.

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Huntington’s disease is a fatal disorder, and despite the gene responsible for it being identified decades ago, there is still no effective treatment or cure.

The Lund University team believes their new method could improve the success of research into Huntington’s disease and several other neurodegenerative disorders.

Reprogrammed Skin Cells

In this study, led by Johan Jakobsson, a professor of neuroscience at Lund University, the researchers obtained skin biopsies from individuals with Huntington’s disease. They then reprogrammed these skin cells into neurons and compared them with reprogrammed neurons from people without the disorder.

The research team observed several defects in the neurons from Huntington’s disease patients. These findings may help clarify some of the underlying mechanisms of the disorder.

“Among other things, we observed that neurons from patients with Huntington’s disease have problems breaking down and recycling certain proteins, which can lead to energy deficits in these cells,” Jakobsson said.

The scientists also measured the biological age of the neurons created from skin cells. They found that the neurons retained their original biological age, meaning that the reprogrammed neurons were old. This makes the method particularly useful for studying age-related brain disorders, according to Jakobsson.

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He believes their model will provide more insight into Huntington’s disease than animal models and could help researchers discover effective treatments.

Final Thoughts

The new method developed by Lund University researchers offers a more practical approach to studying Huntington’s disease by using reprogrammed aged neurons. This model provides a clearer understanding of the disease’s mechanisms, which may aid future research efforts into neurodegenerative conditions.

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References

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