Publications

Latest publication 02/01/2012

_-Synuclein levels modulate Huntington's disease in mice-

_-Synuclein and mutant huntingtin are the major constituents of the intracellular aggregates that characterize the pathology of Parkinson's disease...

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    [title] => _-Synuclein levels modulate Huntington's disease in mice- 
    [paragraph] => _-Synuclein levels modulate Huntington's disease in mice. 
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Authors
S. Corrochano, M. Renna, S. Carter, N. Chrobot, R. Kent et al.

 Lab
MRC Mammalian Genetics Unit, Harwell, Oxfordshire, UK.
Journal
Human Molecular genetics
Abstract
_-Synuclein and mutant huntingtin are the major constituents of the intracellular aggregates that characterize the pathology of Parkinson's disease (PD) and Huntington's disease (HD), respectively. _-Synuclein is likely to be a major contributor to PD, since overexpression of this protein resulting from genetic triplication is sufficient to cause human forms of PD. We have previously demonstrated that wild-type _-synuclein overexpression impairs macroautophagy in mammalian cells and in transgenic mice. Overexpression of human wild-type _-synuclein in cells and Drosophila models of HD worsens the disease phenotype. Here, we examined whether _-synuclein overexpression also worsens the HD phenotype in a mammalian system using two widely used N-terminal HD mouse models (R6/1 and N171-82Q). We also tested the effects of _-synuclein deletion in the same N-terminal HD mouse models, as well as assessed the effects of _-synuclein deletion on macroautophagy in mouse brains. We show that overexpression of wild-type _-synuclein in both mouse models of HD enhances the onset of tremors and has some influence on the rate of weight loss. On the other hand, _-synuclein deletion in both HD models increases autophagosome numbers and this is associated with a delayed onset of tremors and weight loss, two of the most prominent endophenotypes of the HD-like disease in mice. We have therefore established a functional link between these two aggregate-prone proteins in mammals and provide further support for the model that wild-type _-synuclein negatively regulates autophagy even at physiological levels.
BIOSEB Instruments Used
Grip strength test (BIO-GS3)
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An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.
New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

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