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Breaking Down The Potential Molecular Mechanisms Underlying Parkinson Disease

Date:
January 7, 2008
Source:
Journal of Clinical Investigation
Summary:
New data generated in vitro and in cultured cell lines and mouse neurons has shed light on the mechanisms by which the protein alpha-synuclein is degraded in brain cells known as neurons. This has implications for the development of the neurodegenerative disorder Parkinson disease (PD) because altered degradation of alpha-synuclein has been implicated as a key step in the development of the disorder.

New data generated in vitro and in cultured cell lines and mouse neurons, by Ana Maria Cuervo and colleagues at the Albert Einstein College of Medicine, New York, has shed light on the mechanisms by which the protein alpha-synuclein is degraded in brain cells known as neurons.

This has implications for the development of the neurodegenerative disorder Parkinson disease (PD) because altered degradation of alpha-synuclein has been implicated as a key step in the development of the disorder.

In the study, posttranslational modification of alpha-synuclein by processes such as by phosphorylation and nitration was shown to impair degradation of this protein by a mechanism known as chaperone-mediated autophagy (CMA) in isolated lysosomes, cultured dopaminergic cell lines, and cultured mouse neurons. Of relevance to PD, in which most of the neurons lost are dopaminergic neurons of the substantia nigra, dopamine-modified alpha-synuclein was poorly degraded by CMA and blocked the degradation of other proteins by CMA.

The authors therefore suggested that dopamine-induced inhibition of alpha-synuclein degradation by CMA increases the vulnerability of dopaminergic neurons to cellular stressors, thereby explaining the selective loss of dopaminergic neurons in individuals with PD.

Journal article: Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. Journal of Clinical Investigation. January 2, 2008.


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Journal of Clinical Investigation. "Breaking Down The Potential Molecular Mechanisms Underlying Parkinson Disease." ScienceDaily. ScienceDaily, 7 January 2008. <www.sciencedaily.com/releases/2008/01/080102222921.htm>.
Journal of Clinical Investigation. (2008, January 7). Breaking Down The Potential Molecular Mechanisms Underlying Parkinson Disease. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2008/01/080102222921.htm
Journal of Clinical Investigation. "Breaking Down The Potential Molecular Mechanisms Underlying Parkinson Disease." ScienceDaily. www.sciencedaily.com/releases/2008/01/080102222921.htm (accessed September 2, 2014).

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