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February 9, 2017

Protein Trafficking Roadblocks Could Be Cause of Neurodegeneration

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    Pictured is the cerebellar region of the brain of a mouse lacking the Golgi protein GM130 with the Purkinje neurons labeled in green and DNA in blue. There is loss of Purkinje neurons in the lobes on the right-hand side, which results in inability to coordinate muscle movement (ataxia). [Martin Lowe/The University of Manchester]

    A new collaborative study from investigators at the Chinese Academy of Sciences and the University of Manchester has just uncovered that shutting down the flow of proteins within a uniquely named cell organelle—the Golgi apparatus—could be a major underlying cause of neurodegeneration. The team of researchers examined the role of the Golgi apparatus in neurons and found that mice in which the organelle was disabled suffered from developmental delay, severe ataxia, and postnatal death.

    The Golgi is a compartment inside all cells that controls the processing and transport of proteins. It is fundamental to the growth of the cell membrane and for the release of many types of proteins, such as hormones, neurotransmitters, and the proteins that make up skeletal tissue. While the function of the Golgi apparatus, eponymously named after its Italian discoverer Camillo Golgi, is well understood, it has not been previously shown to have a role in neurodegeneration. With these results, the scientists think they may have found a new avenue to explore in the search for the causes of some neurodegenerative diseases.

    "Our results, combined with previous work, suggest that during the cellular changes that occur, loss of the Golgi function could be an important intermediary step that contributes to cell death,” explained co-senior study author Martin Lowe, Ph.D., professor in the division of molecular and cellular function at the University of Manchester.

    The findings from this study were published recently in the Proceedings of the National Academy of Science in an article entitled “Loss of the Golgin GM130 Causes Golgi Disruption, Purkinje Neuron Loss, and Ataxia in Mice.”

    “Here we report that targeted loss of the golgin GM130 leads to a profound neurological phenotype in mice,” the authors wrote. “Global KO [knockout] of mouse GM130 results in developmental delay, severe ataxia, and postnatal death. We further show that selective deletion of GM130 in neurons causes fragmentation and defective positioning of the Golgi apparatus, impaired secretory trafficking, and dendritic atrophy in Purkinje cells. These cellular defects manifest as reduced cerebellar size and Purkinje cell number, leading to ataxia. Purkinje cell loss and ataxia first appear during postnatal development but progressively worsen with age.”

    Ataxia is a term for a group of disorders that affect coordination, balance, and speech. Any part of the body can be affected, but patients with ataxia often have difficulties with balance and walking, speaking, swallowing, tasks such as writing and eating, and vision. It can be inherited or brought on through incidents such as a stroke or through old age.

    How much the Golgi apparatus contributes to the major neurodegenerative diseases such as Alzheimer's or Parkinson's is something that is currently unclear, though other studies have made this link.

    "Together with other published work, our findings suggest that in certain neurodegenerative diseases the loss of function of the Golgi apparatus may contribute to the pathology that is occurring,” Dr. Lowe concluded.

     

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