Tech UPTechnologyParkinson's, discover brain changes that indicate its early onset

Parkinson's, discover brain changes that indicate its early onset

Parkinson’s is one of the best known and most frequent neurodegenerative diseases , whose cause remains an unsolved mystery to this day.

Its appearance takes place long before the first symptoms begin to show their face. At the time of diagnosis, there is already a 50-60% loss of dopaminergic neurons (those affected in this disease). For this reason, it is necessary to find signs that allow the disease to be identified long before a patient begins to show the first symptoms, which in medicine is known as early detection or early diagnosis.

Recently, a new study has been published in the journal Brain in which they have identified different functional changes in the brain at a physiological and molecular level that take place even before the neurons begin to degenerate and the first symptoms appear.

The study, carried out by a group of researchers from the Cima University of Navarra, has made it possible to find these possible identifying signs – also known as biomarkers – that help detect the disease earlier. In addition, it is a first step to develop neuroprotective therapies that help prevent the disease. How was this discovery possible?

A useful model of Parkinson’s in the laboratory

To study the different diseases that affect us today – such as neurodegenerative diseases, cardiovascular diseases, diabetes or cancer, among others – and to be able to apply advances in the clinic, it is necessary to carry out previous studies with laboratory models.

Cima researchers developed a rat animal model that develops Parkinson’s disease in order to study how it evolves from its earliest stages.

Thanks to this, the researchers verified that, after four weeks, the animals showed a 30% loss of the neurons affected by this disease. However, they had not yet shown any symptoms. ”In this pre-symptomatic phase is when the dopaminergic neuron is dying en masse without us knowing it and it is in this phase that we are interested in being able to act” – explains Dr. María Cruz Rodríguez-Oroz, director of the Neuroscience Program at Cima and the Department of Neurology of the University Clinic of Navarra and director of the work.

New identifying signs of the disease

Detecting a disease in the initial phases of its development is one of the ways that exist to be able to treat it with a greater probability of success or, failing that, to be able to control it to alleviate the symptoms and make progress more gradual.

In the case of some untreated neurodegenerative diseases, such as Parkinson’s, finding ways to prevent and alleviate the effects of the disease is still one of the great challenges facing scientific research.

The researchers focused their work on a specific area of neurons: the place where synapses are produced (the connections between neurons through which they communicate with each other). The reason for this is that this part is the first to be affected when neuronal damage occurs, and the “disconnection” of this process (synaptic deterioration) could precede the degeneration of neurons in Parkinson’s.

This approach has allowed the group of scientists to identify one of the mechanisms that could be key in the process of initiation and evolution of the disease. As Dr. Rodríguez-Oroz points out – ”Using complex imaging and physiology techniques, we confirm that some early functional changes occur, others later and, finally, structural changes that coincide with the process of neuronal death. All this before the motor manifestations of the disease”.

New key molecules: possible culprits?

In the development of Parkinson’s, there are certain key molecules, such as the so-called α-synuclein, which are altered, forming artifacts and causing damage to the affected area of the brain (the substantia nigra, a structure located in the middle part of the brain). However, other altered molecules, still unknown, could be favoring this neurodegeneration process.

Through molecular analysis, the group of researchers has identified other molecules involved in key processes for brain cells such as metabolism (fundamental in energy production) or the neuron vesicle cycle (the process in which and they recycle the packages where said cells accumulate the messages that they will send to their companions). Processes, which, ultimately, are essential for the health of neurons.

Thanks to this, they observed that an energy failure and the accumulation of dysfunctional components seem to be the first two events that occur in the area of the neuron in charge of sending the message. Both events appear to precede structural changes in these cells and their subsequent death.

The discovery of altered molecules that are key in these abnormal events can set a precedent to: on the one hand have indicators that allow early identification of the disease and, on the other hand, present these molecules as a possible weak point that can be targeted with pharmacological treatments that would counteract the degeneration of these neurons in order to delay or prevent the development of Parkinson’s disease. “We will modify them through advanced therapies, such as gene therapy or small molecules, that act on them. The objective is to restore the function of the synapse and avoid the late functional and structural changes that we see in the synapse” – explains Dr. Rodríguez-Oroz.

April 11: World Parkinson’s Day

Today, April 11, is World Parkinson’s Day. A commemorative day in which it is essential to remember that neurodegenerative diseases continue to be one of the main causes of death in the world. Specifically, Parkinson’s is the second most prevalent disease today after Alzheimer’s and belongs to the so-called movement disorders.

Despite their complexity, neurodegenerative diseases continue to be an objective that can only be tackled in the coming years in the hands of research.

References:

Spanish Parkinson Federation. What is Parkinson’s?

Merino-Galan, L. et al. 2022. Striatal synaptic bioenergetic and autophagic decline in premotor experimental parkinsonism. Brain. DOI: https://doi.org/10.1093/brain/awac087
QUIEN. 2020. The 10 leading causes of death
 
 

 

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