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APP96-110 Elicits Neuroprotective Effects Following Ischemic Insult in Animal Models

Authors
 Renée Kosonen  ;  Ji Young Chang  ;  Seowoo Lee  ;  Jiwon Kim  ;  Jong Youl Kim  ;  Jong Eun Lee 
Citation
 NEUROCHEMICAL RESEARCH, Vol.48(8) : 2568-2579, 2023-08 
Journal Title
NEUROCHEMICAL RESEARCH
ISSN
 0364-3190 
Issue Date
2023-08
MeSH
Amyloid beta-Protein Precursor / metabolism ; Animals ; Anti-Inflammatory Agents / therapeutic use ; Infarction, Middle Cerebral Artery / drug therapy ; Infarction, Middle Cerebral Artery / metabolism ; Ischemic Stroke* ; Mice ; Models, Animal ; Neuroinflammatory Diseases ; Neuroprotective Agents* / metabolism ; Neuroprotective Agents* / pharmacology ; Neuroprotective Agents* / therapeutic use ; Phosphatidylinositol 3-Kinases / metabolism ; Rats ; Rats, Sprague-Dawley ; Stroke*
Keywords
APP96-110 ; Amyloid precursor protein ; Ischemic stroke ; Microglia ; Neuroinflammation
Abstract
Competitive amyloidogenic pathways play an important role in many neurological diseases such as the onset of various degenerative diseases and ischemic stroke. Overexpression of amyloid precursor protein (APP) and amyloid-beta is modulated via the amyloidogenic pathway, which plays a crucial role in neuroinflammation. During ischemic conditions, the activity of the anti-inflammatory non-amyloidogenic pathway decreases, thus increasing the activity of amyloidogenic pathway. The soluble alpha form of APP (sAPP alpha), formed via the non-amyloidogenic pathway, exhibits neuroprotective effects against neurological diseases. sAPP alpha is thought to have a modulatory effect on several cell survival pathways, including its ability to inhibit the phosphoinositide 3-kinases (PI3K) pathway, thereby inhibiting the inflammatory response. The APP derivative, APP96-110, could act as a functional substitute for native sAPP alpha. Herein, we investigated whether APP96-110 has neuroprotective effects against neuroinflammation and damage following cerebral ischemic stroke. Treatment with diluted APP96-110 (0.005 mg/kg) in mice after 30 min of transient middle cerebral artery occlusion (tMCAO) showed improved motor function and reduced expression of the inflammatory marker CD86. APP96-110 decreased the infarct size and induced an anti-inflammatory response by inhibiting the PI3K pathway. These results suggest that the treatment of APP96-110 is efficacious in reducing neuroinflammation and infarct size in ischemic stroke.
Full Text
https://link.springer.com/article/10.1007/s11064-023-03928-6
DOI
10.1007/s11064-023-03928-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Youl(김종열) ORCID logo https://orcid.org/0000-0002-8340-2894
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/195499
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