Neurogenesis May Be Impaired By Parkinson's Gene

Specific gene defect linked to Parkinson's disease not only causes the early death of neurons but is also responsible for impairing the process that generates neurons in the brain throughout the lifetime, as per a study at the University of Sheffield's Neuroscience Institute, published in Scientific Reports.

The generation of dopamine-producing neurons relies upon the Parkinson’s gene PINK1 that is also responsible for the premature death of these neurons.

‘Deficiency in a specific gene defect linked to Parkinson's disease, PINK1 results in fewer dopamine-producing neurons that are made throughout life. This helps in the development of treatments and therapies against Parkinson's due to the PINK1 defect that focus on enhancing the generation of new dopamine-producing neurons, rather than just trying to protect these neurons from dying later. ’

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Parkinson's disease is a progressive neurodegenerative disorder that primarily affects movement due to loss of nerve cells – neurons that produce a chemical messenger (neurotransmitter) in the brain called dopamine (black substance). It is characterized by the formation of inclusion proteins called Lewy bodies.

Around 145,000 people in the UK and 10 million people worldwide are said to be affected by Parkinson's disease. The study team utilised two complementary model systems to examine how neurons are produced throughout our lifetime and also to measure how inactivation of the PINK1 gene affects dopamine-producing neurons in the adult brain.

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Depletion of dopamine-producing neurons (due to early death) most commonly occurs due to Parkinson's genes, such as PINK1. It was thereby found that a deficiency in PINK1 results in fewer dopamine-producing neurons that are made throughout life.

"Neurogenesis is the process by which new neurons are formed in the brain. Recent evidence suggests that this process is ongoing throughout life but the relevance of this is poorly understood in neurodegenerative disorders such as Parkinson's disease". "We know that mutations in the PINK1 gene cause an early onset, an inherited form of Parkinson's disease. If we can further our understanding about the impact of this genetic mutation on the dopamine-producing neurons we can develop new therapeutic approaches that aim to mitigate those effects", says Professor Oliver Bandmann, Professor of Movement Disorders Neurology at the Sheffield Institute for Translational Neuroscience (SITraN).

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"This study attests to the power of using simple model organisms for pre-clinical translational research. We used the zebrafish to demonstrate that dopamine-producing neurons are generated into adulthood at a rate that decreases with age and that PINK1-deficiency impairs neurogenesis of these neurons, significantly in early adult life. Our international collaborators then confirmed these results in a human organoid cell model", says Professor Marysia Placzek, Professor of Developmental Neurobiology in the Department of Biomedical Science.

The study thus allows to identify the precise mechanisms that link Parkinson's genes to neurogenesis and help in the development of treatments and therapies that enhances the generation of new dopamine-producing neurons in Parkinson's due to PINK1 defect.

Source-Medindia