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Shaking Parkinson’s off our future

Author: Laura Argelich

Did you know that more than 10 million people worldwide suffer from Parkinson’s disease? To give you a sense of how many people this is, if they were standing one after the other with their arms open, they could cover the distance between Barcelona and Australia. What if I told you, that 8,5 million of these cases got it by chance?

With the aging of global population, neurodegenerative diseases, that are known to be strongly age-related, will gain incidence, having a devastating impact on patients, families and societies. This presents a great challenge for the scientific community, since there’s so much to still unravel about the most complex organ of our bodies, the brain. However, new technologies and discoveries gives us hope for a better future.

Parkinson’s disease (PD) is caused by the loss of a specific type of neurons, known as dopaminergic (DA) neurons, found in a region of the brain named substantia nigra (SN) pars compacta. These cells are important for the control of multiple brain functions including voluntary movement. In fact, PD is well known by its motor symptoms such as tremor, rigidity and postural instability. However, these neurons play also an important role in behavioural processes, affecting mood, reward, addiction, and stress. Nowadays, the neuronal loss leading to the disease is still irreversible and the few treatments available, which aim only to treat the symptoms, are not effective after a period of time.

As it has been said in several previous posts on this blog, after development, neurons in brain and spinal cord largely loose the ability to regenerate following traumatic injuries or neurodegeneration. Even though in the adult brain there are two neurogenic niches, neurons that arise from these regions have very restricted distribution and function in the adult brain and are, therefore, insufficient to repair most of the disrupted neural circuits under pathological conditions.

For decades, a way to repair or promote regeneration within the adult brain has been studied. Most approaches, as pointed out by my fellow ESR11 Fran, are based in two strategies: cell therapies and direct reprogramming. Despite both aim at restoring a tissue or an organ function, the first is based on transplantation of pre-differentiated cells, while the latter on the conversion of non-neuronal cells into neurons in situ.

In my project, I am working to develop a new therapeutic strategy to offer an alternative treatment to fight PD. My approach is based on trying to efficiently convert mouse astrocytes into induced DA neurons in vivo to replace lost dopaminergic population.

In parallel, I am performing a range of experiments to describe and dissect better the alterations that this specific population suffers during disease. It’s known that manifestations of PD appear once around 60% of DA neurons in the SN have been lost, meaning that for a period of time, remaining neurons are able to compensate this loss. The process by which they do it, however, is still to be unravelled. Trying to throw some light in this matter, I am working to explore if the axonal terminals suffer a remodelling during neurodegeneration by developing a single neuronal labelling tool.

In all, I hope to contribute a little bit in understanding the pathophysiology of PD to advance towards the development of new therapies, aiming to improve the quality of life of patients and families.

Learn from yesterday, live for today, hope for tomorrow. The important thing is not to stop

questioning.” – Albert Einstein

References and links:

Barker, R., Götz, M., & Parmar, M. (2018). New approaches for brain repair—from rescue to

reprogramming. Nature, 557(7705), 329-334. doi: 10.1038/s41586-018-0087-1

Chinta, S., & Andersen, J. (2005). Dopaminergic neurons. The International Journal Of Biochemistry & Cell Biology, 37(5), 942-946. doi: 10.1016/j.biocel.2004.09.009

Mattugini, N., Bocchi, R., Scheuss, V., Russo, G. L., Torper, O., Lao, C. L., & Götz, M. (2019).

Inducing Different Neuronal Subtypes from Astrocytes in the Injured Mouse Cerebral Cortex. Neuron, 103(6), 1086- 1095.e5.

Wyss-Coray, T. (2016). Ageing, neurodegeneration and brain rejuvenation. Nature, 539(7628), 180-186. doi: 10.1038/nature20411

The challenge of neurodegenerative diseases in an aging population. (2017). Retrieved 28 January 2021, from GB&hash=C665B04DAB77DE2C0 53D8F51E61E4379

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