Zigao Wang, Lu Xiong, Wenbin Wan, Lijie Duan, Xiaojing Bai, Hengbing Zu
Abstract
Alzheimer's disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks. Our data showed that intranasal BMP9 administration significantly improved the spatial and associative learning and memory of APP/PS1 mice. We also found that intranasal BMP9 administration significantly reduced the amyloid β (Aβ) plaques overall, inhibited tau hyperphosphorylation, and suppressed neuroinflammation in the transgenic mouse brain. Furthermore, intranasal BMP9 administration significantly promoted the expression of low-density lipoprotein receptor-related protein 1 (LRP1), an important membrane receptor involved in the clearance of amyloid β via the blood-brain barrier (BBB), and elevated the phosphorylation levels of glycogen synthase kinase-3β (Ser9), which is considered the main kinase involved in tau hyperphosphorylation. Our results suggest that BMP9 may be a promising candidate for treating AD by targeting multiple key pathways in the disease pathogenesis.
Pharmacology, Toxicology and Pharmaceutical Science
5
15%
Engineering
2
6%
Other
1
3%
Unknown
7
21%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 02 December 2022.
All research outputs
#14,439,452
of 23,243,271 outputs
Outputs from Frontiers in Molecular Neuroscience
#1,535
of 2,956 outputs
Outputs of similar age
#228,474
of 421,572 outputs
Outputs of similar age from Frontiers in Molecular Neuroscience
#52
of 99 outputs
Altmetric has tracked 23,243,271 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,956 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 46th percentile – i.e., 46% of its peers scored the same or lower than it.
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We're also able to compare this research output to 99 others from the same source and published within six weeks on either side of this one. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
