Advanced biological techniques may help shape Parkinson’s treatment

In addition to giving us feelings of reward and satisfaction, dopamine is also important for motor control, concentration, learning, and attention. The importance of dopamine becomes very clear in patients with Parkinson’s disease.

In the brains of these patients, the cells that synthesize and secrete dopamine die. These cells are called dopaminergic neurons and act as little dopamine factories. Mental and physical symptoms in Parkinson’s patients only occur when about half of these cells are gone.

This means that the disease is not detected until multiple lesions have occurred. One of the goals of research into the brain’s dopamine system is to find a way to detect Parkinson’s disease and related diseases at an earlier stage.

Researcher Marte Innselset Flydal, at the department of biomedical sciences, University of Bergen, said: “In this way, you can find drugs that can prevent the disease from developing further.

Understanding how dopamine regulates its production

Enzymes are proteins that catalyze chemical reactions in the body. The three-dimensional structure of enzymes is essential for their activity and regulation. Inside the dopamine-producing cells, there are large amounts of an enzyme called tyrosine hydroxylase (TH).

“Such 3D structures can tell us how cellular processes happen at the atomic level and therefore also how we can find targeted treatments to correct errors in For example, for TH, such mutations cause TH deficiency, says Professor Aurora Martinez, at the department of biomedical science, UiB, a neurological disease is classed as enzymes. into the subgroup of Parkinson’s disease.

In her research group, a partner at the center of Neuro-SysMed, they work to understand how proteins work at the structural level. In other words, they are trying to figure out how mutations cause defects in protein function and how those defects can be corrected.

TH’s dedicated job is to convert the amino acid tyrosine into L-dopa, which is further converted to dopamine by another enzyme. It is well known that TH is an important enzyme in the regulation of dopamine synthesis, but it is not yet understood how this occurs at the level of structural detail.

It has long been known that dopamine can regulate its production. Dopamine can bind to the TH enzyme and inactivate it. Such a regulatory mechanism is called negative feedback and ensures that dopamine synthesis is turned off when the cell has enough dopamine.

“When dopamine levels drop again, signaling pathways are activated in the cell,” said lead researcher Rune Kleppe at the school. research.

It is the interplay between these regulatory mechanisms that researchers now believe they can understand on a detailed level.

“This knowledge gives us new opportunities to develop drugs for neuropsychiatric and neurodegenerative diseases,” said Professor Martinez.

Using complex methods

These research results are the product of longstanding and world-leading research in TH at the Faculty of Biomedical Sciences (UiB) and Helse Bergen, and in protein structure in the research group of Professor José María Valpuesta at Professor José María Valpuesta at Centro Nacional de Biotecnología (CNB-CSIC) in Madrid, uses sophisticated high-resolution electron microscopy to determine the three-dimensional structure of proteins.

“Electron microscopy is essential to understand what TH looks like and also to see how it changes when it binds to dopamine,” says Martinez.

Source: Eurekalert


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