Dataset Information
Ligustilide-loaded liposome ameliorates mitochondrial impairments and improves cognitive function via the PKA/AKAP1 signaling pathway in a mouse model of Alzheimer's disease.
Ontology highlight
ABSTRACT: Background
Oxidative stress is an early event in the development of Alzheimer's disease (AD) and maybe a pivotal point of interaction governing AD pathogenesis; oxidative stress contributes to metabolism imbalance, protein misfolding, neuroinflammation and apoptosis. Excess reactive oxygen species (ROS) are a major contributor to oxidative stress. As vital sources of ROS, mitochondria are also the primary targets of ROS attack. Seeking effective avenues to reduce oxidative stress has attracted increasing attention for AD intervention.Methods
We developed liposome-packaged Ligustilide (LIG) and investigated its effects on mitochondrial function and AD-like pathology in the APPswe/PS1dE9 (APP/PS1) mouse model of AD, and analyzed possible mechanisms.Results
We observed that LIG-loaded liposome (LIG-LPs) treatment reduced oxidative stress and β-amyloid (Aβ) deposition and mitigated cognitive impairment in APP/PS1 mice. LIG management alleviated the destruction of the inner structure in the hippocampal mitochondria and ameliorated the imbalance between mitochondrial fission and fusion in the APP/PS1 mouse brain. We showed that the decline in cAMP-dependent protein kinase A (PKA) and A-kinase anchor protein 1 for PKA (AKAP1) was associated with oxidative stress and AD-like pathology. We confirmed that LIG-mediated antioxidant properties and neuroprotection were involved in upregulating the PKA/AKAP1 signaling in APPswe cells in vitro.Conclusion
Liposome packaging for LIG is relatively biosafe and can overcome the instability of LIG. LIG alleviates mitochondrial dysfunctions and cognitive impairment via the PKA/AKAP1 signaling pathway. Our results provide experimental evidence that LIG-LPs may be a promising agent for AD therapy.
SUBMITTER: Zhang Q
PROVIDER: S-EPMC10916432 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
Publications
Ligustilide-loaded liposome ameliorates mitochondrial impairments and improves cognitive function via the PKA/AKAP1 signaling pathway in a mouse model of Alzheimer's disease.
CNS neuroscience & therapeutics 20230917 3
<h4>Background</h4>Oxidative stress is an early event in the development of Alzheimer's disease (AD) and maybe a pivotal point of interaction governing AD pathogenesis; oxidative stress contributes to metabolism imbalance, protein misfolding, neuroinflammation and apoptosis. Excess reactive oxygen species (ROS) are a major contributor to oxidative stress. As vital sources of ROS, mitochondria are also the primary targets of ROS attack. Seeking effective avenues to reduce oxidative stress has att ...[more]