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Longevity Briefs: A Step Closer To Understanding Parkinson’s Disease?

Posted on 8 October 2021

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Progressive injury and loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies (the aggregation of misfolded proteins within neurons) are classic characteristics of Parkinson’s disease. Unfortunately, our understanding of the molecular causes of these changes is lacking, which makes developing treatments for the disease more challenging. One possible mechanism, whose involvement in Parkinson’s disease is currently uncertain, is the impairment of the secretory granules – large vesicles within the cell where hormones and neurotransmitters like dopamine are processed, sorted and stored.

What did the researchers do: In this study, researchers looked at the number of secretory granules in a mouse model of MPTP-induced Parkinson’s disease compared with controls. They then isolated secretory granules from the dopaminergic neurons of the mice and studied how protein expression differed between the Parkinson’s mice and the controls.

Key takeaway(s) from this research: In the mice with induced Parkinson’s disease, the number of secretory granules was significantly reduced compared with controls. The researchers identified 536 proteins that were expressed at significantly different levels in the secretory granules of Parkinson’s mice compared with controls. Analysis of these proteins and their interactions suggested that the complex network of proteins that make up the secretory granules’ signalling and processing machinery was compromised in the MPTP-treated mice.

Image showing dopaminergic neurons (green) and secretory granules (red) in the ventral tegmental area (VTA) and substantia nigra par compacta (SNpc) of control mice and MPTP-treated mice.

This points towards disruption of neuropeptide processing in the secretory granules as potentially being part of the pathology of Parkinson’s disease. However, it’s important to remember that the mice in this study were dosed with MPTP, which is essentially a neurotoxin that destroys dopaminergic neurons to produce a Parkinson’s-like disease over a short timespan. Most cases of Parkinson’s disease in humans develop slowly over the course of many years, and there is no guarantee that a mechanism important in a rather extreme, accelerated animal form of the disease will be important in humans.

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      Proteomic characterization of secretory granules in dopaminergic neurons indicates chromogranin/secretogranin-mediated protein processing impairment in Parkinson’s disease:

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