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A brain-targeted, modified neurosin (kallikrein-6) reduces α-synuclein accumulation in a mouse model of multiple system atrophy

Overview of attention for article published in Molecular Neurodegeneration, September 2015
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Title
A brain-targeted, modified neurosin (kallikrein-6) reduces α-synuclein accumulation in a mouse model of multiple system atrophy
Published in
Molecular Neurodegeneration, September 2015
DOI 10.1186/s13024-015-0043-6
Pubmed ID
Authors

Brian Spencer, Elvira Valera, Edward Rockenstein, Margarita Trejo-Morales, Anthony Adame, Eliezer Masliah

Abstract

Multiple system atrophy (MSA) is a progressive, neurodegenerative disease characterized by parkinsonism, resistance to dopamine therapy, ataxia, autonomic dysfunction, and pathological accumulation of α-synuclein (α-syn) in oligodendrocytes. Neurosin (kallikrein-6) is a serine protease capable of cleaving α-syn in the CNS, and we have previously shown that lentiviral (LV) vector delivery of neurosin into the brain of a mouse model of dementia with Lewy body/ Parkinson's disease reduces the accumulation of α-syn and improves neuronal synaptic integrity. In this study, we investigated the ability of a modified, systemically delivered neurosin to reduce the levels of α-syn in oligodendrocytes and reduce the cell-to-cell spread of α-syn to glial cells in a mouse model of MSA (MBP-α-syn). We engineered a viral vector that expresses a neurosin genetically modified for increased half-life (R80Q mutation) that also contains a brain-targeting sequence (apoB) for delivery into the CNS. Peripheral administration of the LV-neurosin-apoB to the MBP-α-syn tg model resulted in accumulation of neurosin-apoB in the CNS, reduced accumulation of α-syn in oligodendrocytes and astrocytes, improved myelin sheath formation in the corpus callosum and behavioral improvements. Thus, the modified, brain-targeted neurosin may warrant further investigation as potential therapy for MSA.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Denmark 1 2%
Unknown 44 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 24%
Student > Master 11 24%
Researcher 5 11%
Student > Doctoral Student 3 7%
Professor > Associate Professor 3 7%
Other 6 13%
Unknown 7 15%
Readers by discipline Count As %
Neuroscience 10 22%
Agricultural and Biological Sciences 8 17%
Medicine and Dentistry 4 9%
Biochemistry, Genetics and Molecular Biology 4 9%
Computer Science 2 4%
Other 7 15%
Unknown 11 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 September 2015.
All research outputs
#3,014,107
of 6,395,452 outputs
Outputs from Molecular Neurodegeneration
#227
of 326 outputs
Outputs of similar age
#108,070
of 200,749 outputs
Outputs of similar age from Molecular Neurodegeneration
#21
of 23 outputs
Altmetric has tracked 6,395,452 research outputs across all sources so far. This one is in the 29th percentile – i.e., 29% of other outputs scored the same or lower than it.
So far Altmetric has tracked 326 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.5. This one is in the 20th percentile – i.e., 20% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 200,749 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 4th percentile – i.e., 4% of its contemporaries scored the same or lower than it.