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Dear Doctor  


In 2010, more than 800 publications resulted from studies on the LRRK2 (Leucine-rich repeat kinase 2) protein. This year looks like this focus will be continued as over 100 publications have already appeared in the first 6 weeks of 2011. Why the interest?


LRRK2 (also now classified as PARK8) became of great interest in 2004 when it was identified as the second autosomal dominant Parkinson's disease (PD) gene involving a toxic gain of function. Mutations in the LRRK2 gene account for approximately 6% of all familial cases of PD as well as 2% of spontaneous cases. The LRRK2 gene encodes a protein that is part of a larger multidomain protein with GTPas and kinase domains. Only a few of its substrates have been identified, so its role in triggering this disease remains an enigma. The best evidence suggests that mutated LRRK2 is toxic due to an enhanced kinase activity (Lee et al, Nature Med 16:998-1000, 2010).

 

A novel approach to generating animal models of Parkinson's disease  

A rat model of progressive nigral neurodegeneration induced by the Parkinson's disease-associated G2019S mutation in LRRK2. Dusonchet et al, The Journal of Neuroscience 2011 31:907-912 Abstract

 

Producing transgenic animals is now routine, but their value is often limited by inability to target expression to specific groups of cells, including neurons, as well as the complexity of using animals other than mice. In this brief communication, these researchers have used an alternate viral approach to deliver a mutant LRRK2 gene to neurons within the nigrostriatal system of adult rats. The result is a useful rat model of PD that can be generated quickly in most laboratories.

 

LRRK2 kinase inhibition is protective in PD animal models 

Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease  Lee et al, Nature Medicine 2010 Sep;16(9):998-1000 Abstract 

 

That LRRK2 mutations generate a toxic gain of function, possibly as a result of increased kinase activity, suggests that specific kinase inhibitors might prevent LRRK2-induced degeneration. This study provides evidence in both in vitro and in vivo models that the neuronal degeneration seen in these models is due to the enhanced kinase activity of the mutant LRRK2 protein. It also points the way to potential treatments for this form of PD.

 

Two new reviews suggest intersecting pathways for LRRK2 and alpha-synuclein 
Leucine-rich repeat kinase 2 and alpha-synuclein: intersecting pathways in the pathogenesis of Parkinson's disease?  Greggio et al, Molecular Neurodegeneration 2011 6Jan 18;6(1):6 Abstract 

This excellent review discusses recent literature on these two genes which both cause dominantly inherited PD, and looks for any evidence that suggests a functional link between them. The authors provide a cogent argument for an action of LRRK2 in promoting alpha-synuclein aggregation.

 

The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease  Cookson MR, Nature Reviews, Neuroscience Dec 2010 11(12):791-7 Abstract   


In this review, Cookson also argues the case for an intersection between LRRK2 and alpha-synuclein. He adds the possible involvement of tau protein in trying to understand the disease process.

Hot topics in LRRK2 research
A novel approach to generating animal models of Parkinson's disease
LRRK2 kinase inhibition is protective in PD animal models
Two new reviews suggest intersecting pathways for LRRK2 and alpha-synuclein
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*New* LRRK2 antibodies

from Biosensis 

R-183-50 

 


 

 

 

 

 

Rabbit antibody to human LRRK2 R-183-50 A synthetic peptide corresponding to amino acids 946 - 962 of the human LRRK2 protein conjugated to diptheria toxin was used as the immunogen.This antibody stains LRRK2 positive tangles in inferior temporal cortex of  human brain affected by Alzheimer's disease. 

 

Sheep antibody to LRRK2

S-070-1000 A synthetic peptide corresponding to amino acids 946-962 of human LRRK2 protein conjugated to the Blue Carrier Protein has been used as the immunogen.

Other quality antibodies for Parkinson's research

In addition to LRRK2, Biosensis stocks a wide range of quality antibodies for research on Parkinson's and associated diseases:

 

R-114-100 Rabbit anti-parkin (295-311 aa). See reference in  Song et al (2009) 

 

R-075-100 Rabbit anti-alpha synuclein (129-140 aa). See reference in  Tinsley et al (2010) 

 

S-075-50  Sheep anti-alpha synuclein (116-131 aa). See references in Kuo et al (2010), Pelkonen et al (2010) and 

Lou et al (2010)

 

R-060-100 Rabbit anti-pan synuclein. See reference in Ulusoy et al (2010) and 

Naasstrom et al (2010)

 

R-182-250 Rabbit anti-ubiquitin

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Should your manuscript ever be rejected by ANY journal because of insufficient information about a Biosensis antibody, we will gladly refund TWICE the purchase price of that antibody!




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Our staff have over 60 years experience in manufacturing and using antibodies and over 340 peer reviewed research publicationsIf you have any questions, one of our experienced researchers is always there to help at biospeak@biosensis.com.

Until next time, good luck with your research.


Sincerely,
 
Tina


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