ScienceDaily (Mar. 7, 2008) — The pathological mediators of neurodegeneration in Parkinson's disease (PD) are unknown. One hypothesis postulates that neurodegeneration results from proteolytic stress due to accumulation and aggregation of misfolded or overexpressed proteins.

In support of this, mutations and duplications of the ±-synuclein gene are found in some PD families, and aggregates of ±-synuclein in cytoplasmic inclusions (Lewy bodies) are a hallmark of PD. 

Researchers report the development of transgenic mice that conditionally overexpress ±-synuclein.

The mice showed progressive loss of motor and cognitive function and some degeneration of hippocampal neurons and of dopaminergic neurons in the substantia nigra. Although cell death occurred in the substantia nigra, levels were below statistical significance, and most was not apoptotic as is seen in PD. ±-Synuclein aggregated but did not form Lewy bodies.

Interestingly, turning off ±-synuclein overexpression slowed the progression of motor dysfunction but did not alter cellular pathology.

Journal article:  Silke Nuber, Elisabeth Petrasch-Parwez, Beate Winner, Jürgen Winkler, Stephan von Hörsten, Thorsten Schmidt, Jana Boy, Melanie Kuhn, Huu P. Nguyen, Peter Teismann, Jörg B. Schulz, Manuela Neumann, Bernd J. Pichler, Gerald Reischl, Carsten Holzmann, Ina Schmitt, Antje Bornemann, Wilfried Kuhn, Frank Zimmermann, Antonio Servadio, and Olaf Riess. "Conditional Model of Parkinson's Disease" was published in the Journal of Neuroscience in March of 2008.

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