Study explores neuronal homeostasis

Autophagy linked to gated calcium channel

ALEX HABER
Staff Writer

Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, plague society today, and too few cures or treatments exist to make an impact on the afflicted. The issue arises in part from our lack of knowledge as to just how these diseases operate on a cellular and molecular basis. PLoS Biology published an article entitled “A Voltage-Gated Calcium Channel Regulates Lysosomal Fusion with Endosomes and Autophagosomes and is Required for Neuronal Homeostasis” on March 25. The article explores the function of receptor proteins involved in the process of autophagy. The study aims to develop a different mechanism in which certain neurological diseases might occur.

Autophagy is the process of destruction of cellular waste. Waste might include anything from messenger RNA to defunct mitochondria. First, the materials designated for digestion are encased within a vacuole called an autophagosome. The autophagosome then binds to a lysosome. A lysosome is a small organelle containing hydrolytic enzymes necessary for digestion. The autophagosome and the lysosome fuse together and mix their contents. Voltage-gated calcium channels (VGCC) control the fusion of the two vacuoles. Following digestion, the contents are released back out into the cell. The cell reuses the contents in the assembling of other cellular components. The researchers took a closer look at the role of VGCC by inhibiting its function.

The model system used for the study was a mouse. The mice were bred to be homozygous for the ducky gene. The ducky gene in mice corresponds to several neurological diseases such as ataxia, or inability to coordinate muscle movement and epilepsy. Researchers found that the gene corresponded to the loss of functional capability for the VGCC. The discovery gives key insight into how the neurological diseases may damage the nervous system.

In the case of the arrest of VGCC function, the article found that significant degeneration occurred in the brains of mice with the ducky gene. The degeneration occurs from the cells’ inability to remove harmful and defunct constituents in the cytosol. The buildup causes the cytosol to become toxic and necrosis to occur.

The findings are just a stepping stone to uncovering the complexity of neurological disease. By unraveling the mystery we can create new therapeutic techniques that may serve as a treatment or cure for a number of debilitating diseases.

The study was conducted at the Life Sciences Institute and Innovation Center of Cell Biology at Zheijang Univeristy in China. The first author of the article was Xuejan Tian, Ph.D.

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