| Title |
Targeted Gene Editing of Glia Maturation Factor in Microglia: a Novel Alzheimer’s Disease Therapeutic Target
|
|---|---|
| Published in |
Molecular Neurobiology, April 2018
|
| DOI | 10.1007/s12035-018-1068-y |
| Pubmed ID | |
| Authors |
Sudhanshu P. Raikwar, Ramasamy Thangavel, Iuliia Dubova, Govindhasamy Pushpavathi Selvakumar, Mohammad Ejaz Ahmed, Duraisamy Kempuraj, Smita A. Zaheer, Shankar S. Iyer, Asgar Zaheer |
| Abstract |
Alzheimer's disease (AD) is a devastating, progressive neurodegenerative disorder that leads to severe cognitive impairment in elderly patients. Chronic neuroinflammation plays an important role in the AD pathogenesis. Glia maturation factor (GMF), a proinflammatory molecule discovered in our laboratory, is significantly upregulated in various regions of AD brains. We have previously reported that GMF is predominantly expressed in the reactive glial cells surrounding the amyloid plaques (APs) in the mouse and human AD brain. Microglia are the major source of proinflammatory cytokines and chemokines including GMF. Recently clustered regularly interspaced short palindromic repeats (CRISPR) based genome editing has been recognized to study the functions of genes that are implicated in various diseases. Here, we investigated if CRISPR-Cas9-mediated GMF gene editing leads to inhibition of GMF expression and suppression of microglial activation. Confocal microscopy of murine BV2 microglial cell line transduced with an adeno-associated virus (AAV) coexpressing Staphylococcus aureus (Sa) Cas9 and a GMF-specific guide RNA (GMF-sgRNA) revealed few cells expressing SaCas9 while lacking GMF expression, thereby confirming successful GMF gene editing. To further improve GMF gene editing efficiency, we developed lentiviral vectors (LVs) expressing either Streptococcus pyogenes (Sp) Cas9 or GMF-sgRNAs. BV2 cells cotransduced with LVs expressing SpCas9 and GMF-sgRNAs revealed reduced GMF expression and the presence of indels in the exons 2 and 3 of the GMF coding sequence. Lipopolysaccharide (LPS) treatment of GMF-edited cells led to reduced microglial activation as shown by reduced p38 MAPK phosphorylation. We believe that targeted in vivo GMF gene editing has a significant potential for developing a unique and novel AD therapy. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 40% |
| Puerto Rico | 1 | 20% |
| Unknown | 2 | 40% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 60% |
| Scientists | 2 | 40% |
Mendeley readers
The data shown below were compiled from readership statistics for 82 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 82 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 21 | 26% |
| Researcher | 14 | 17% |
| Student > Ph. D. Student | 14 | 17% |
| Student > Master | 5 | 6% |
| Student > Doctoral Student | 3 | 4% |
| Other | 4 | 5% |
| Unknown | 21 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 27 | 33% |
| Neuroscience | 14 | 17% |
| Medicine and Dentistry | 6 | 7% |
| Agricultural and Biological Sciences | 4 | 5% |
| Social Sciences | 3 | 4% |
| Other | 8 | 10% |
| Unknown | 20 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 01 May 2018.
All research outputs
#6,954,635
of 25,157,832 outputs
Outputs from Molecular Neurobiology
#1,395
of 3,906 outputs
Outputs of similar age
#111,363
of 332,521 outputs
Outputs of similar age from Molecular Neurobiology
#46
of 129 outputs
Altmetric has tracked 25,157,832 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 3,906 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one has gotten more attention than average, scoring higher than 64% of its peers.
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 332,521 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
We're also able to compare this research output to 129 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.