• Identification of Cinnamein, a...

*Result*: Identification of Cinnamein, a Component of Balsam of Tolu/Peru, as a New Ligand of PPARα for Plaque Reduction and Memory Protection in a Mouse Model of Alzheimer's Disease.

Title:
Identification of Cinnamein, a Component of Balsam of Tolu/Peru, as a New Ligand of PPARα for Plaque Reduction and Memory Protection in a Mouse Model of Alzheimer's Disease.
Authors:
McKay M; Department of Neurological Sciences, Rush University Medical Center, Chicago, USA., Gorai S; Department of Neurological Sciences, Rush University Medical Center, Chicago, USA., Paidi RK; Department of Neurological Sciences, Rush University Medical Center, Chicago, USA.; Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, USA., Mondal S; Department of Neurological Sciences, Rush University Medical Center, Chicago, USA.; Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, USA., Pahan K; Department of Neurological Sciences, Rush University Medical Center, Chicago, USA.; Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, USA.
Source:
Journal of Alzheimer's disease reports [J Alzheimers Dis Rep] 2024 May 24; Vol. 8 (1), pp. 903-922. Date of Electronic Publication: 2024 May 24 (Print Publication: 2024).
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Sage Publications Country of Publication: United States NLM ID: 101705500 Publication Model: eCollection Cited Medium: Internet ISSN: 2542-4823 (Electronic) Linking ISSN: 25424823 NLM ISO Abbreviation: J Alzheimers Dis Rep Subsets: PubMed not MEDLINE
Imprint Name(s):
Publication: 2024- : [Thousand Oaks, CA] : Sage Publications
Original Publication: Amsterdam : IOS Press, [2017]-
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Contributed Indexing:
Keywords: ADAM10; Alzheimer’s disease; PPARα; TFEB; cinnamein; cognitive function; plaque
Entry Date(s):
Date Created: 20240624 Latest Revision: 20240625
Update Code:
20260130
PubMed Central ID:
PMC11191634
DOI:
10.3233/ADR-230179
PMID:
38910936
Database:
MEDLINE

*Further Information*

*Background: Despite intense investigations, no effective treatment is yet available to reduce plaques and protect memory and learning in patients with Alzheimer's disease (AD), the most common neurodegenerative disorder. Therefore, it is important to identify a non-toxic, but effective, treatment option for AD.
Objective: Cinnamein, a nontoxic compound, is naturally available in Balsam of Peru and Tolu Balsam. We examined whether cinnamein treatment could decrease plaques and improve cognitive functions in 5XFAD mouse model of AD.
Methods: We employed in silico analysis, time-resolved fluorescence energy transfer assay, thermal shift assay, primary neuron isolation, western blot, immunostaining, immunohistochemistry, Barnes maze, T maze, and open field behavior.
Results: Oral administration of cinnamein led to significant reduction in amyloid-β plaque deposits in the brain and protection of spatial learning and memory in 5XFAD mice. Peroxisome proliferator-activated receptor alpha (PPARα), a nuclear hormone receptor, is involved in plaque lowering and increase in hippocampal plasticity. While investigating underlying mechanisms, we found that cinnamein served as a ligand of PPARα. Accordingly, oral cinnamein upregulated the level of PPARα, but not PPARβ, in the hippocampus, and remained unable to decrease plaques from the hippocampus and improve memory and learning in 5XFAD mice lacking PPARα. While A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is one of the drivers of nonamyloidogenic pathway, transcription factor EB (TFEB) is considered as the master regulator of autophagy. Cinnamein treatment was found to upregulate both ADAM10 and TFEB in the brain of 5XFAD mice via PPARα.
Conclusions: Our results suggest that this balsam component may have therapeutic importance in AD.
(© 2024 – The authors. Published by IOS Press.)*

*The authors have no conflict of interest to report.*