Back to Search
Start Over
Selected microRNAs Increase Synaptic Resilience to the Damaging Binding of the Alzheimer’s Disease Amyloid Beta Oligomers
- Source :
- Molecular Neurobiology
- Publication Year :
- 2020
- Publisher :
- Springer US, 2020.
-
Abstract
- Alzheimer’s disease (AD) is marked by synaptic loss (at early stages) and neuronal death (at late stages). Amyloid beta (Aβ) and tau oligomers can target and disrupt synapses thus driving cognitive decay. Non-demented individuals with Alzheimer’s neuropathology (NDAN) are capable of withstanding Aβ and tau toxicity, thus remaining cognitively intact despite presence of AD neuropathology. Understanding the involved mechanism(s) would lead to development of novel effective therapeutic strategies aimed at promoting synaptic resilience to amyloid toxicity. NDAN have a unique hippocampal post-synaptic proteome when compared with AD and control individuals. Potential upstream modulators of such unique proteomic profile are miRNA-485, miRNA-4723 and miRNA-149, which we found differentially expressed in AD and NDAN vs. control. We thus hypothesized that these miRNAs play an important role in promoting either synaptic resistance or sensitization to Aβ oligomer binding. Using an in vivo mouse model, we found that administration of these miRNAs affected key synaptic genes and significantly decreased Aβ binding to the synapses. Our findings suggest that miRNA regulation and homeostasis are crucial for Aβ interaction with synaptic terminals and support that a unique miRNA regulation could be driving synaptic resistance to Aβ toxicity in NDAN, thus contributing to their preserved cognitive abilities. Electronic supplementary material The online version of this article (10.1007/s12035-020-01868-8) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Male
Proteomics
Amyloid
Amyloid beta
Neuroscience (miscellaneous)
Nerve Tissue Proteins
Neuropathology
Hippocampal formation
Real-Time Polymerase Chain Reaction
Hippocampus
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Non-demented with Alzheimer’s neuropathology
Mice
0302 clinical medicine
Alzheimer Disease
Cell Line, Tumor
microRNA
medicine
Animals
Humans
Sensitization
Injections, Intraventricular
Amyloid beta-Peptides
biology
Frontal Lobe
Mice, Inbred C57BL
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
Neurology
Gene Expression Regulation
Synaptic resilience
Proteome
biology.protein
Female
Transcriptome
Neuroscience
Alzheimer’s disease
030217 neurology & neurosurgery
Homeostasis
Synaptosomes
Subjects
Details
- Language :
- English
- ISSN :
- 15591182 and 08937648
- Volume :
- 57
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular Neurobiology
- Accession number :
- edsair.doi.dedup.....a1fdca0b5bda259082900ec67f9216e5