Dataset Information

Intranasal administration of balenine alleviates neurodegeneration and inflammation in a mouse model of Parkinsonâ€™s disease

ABSTRACT: Imidazole dipeptides (IDPs) have physiological properties, including antioxidant, pH-buffering, and metal ion chelating activities. Carnosine, an IDP, shows promise for treating neurodegenerative diseases, including Parkinsonâ€™s disease (PD). However, carnosine-degrading enzymes limit its bioavailability. To overcome this, we focused on balenine, a carnosine analog featuring a methylated imidazole that is resistant to degradation enzymes. In this study, we established a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP)-induced PD mouse model and administered balenine via nasal drops to target the brain via the olfactory epithelium. The MPTP-induced PD mouse model was evaluated through various behavioral tests and biochemical analyses. Proteomic analysis was used to explore the mechanism underlying the neuroprotective effects of balenine.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Taku Ozaki

PROVIDER: PXD065872 | JPOST Repository | Fri Jun 05 00:00:00 BST 2026

REPOSITORIES: jPOST

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			Action	DRS
	241213_Ozaki_Brain_1_SWATH.wiff	Wiff
	241213_Ozaki_Brain_1_SWATH.wiff.scan	Wiff
	241213_Ozaki_Brain_2_SWATH.wiff	Wiff
	241213_Ozaki_Brain_2_SWATH.wiff.scan	Wiff
	241213_Ozaki_Brain_3_SWATH.wiff	Wiff

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Balenine alleviates neurodegeneration and inflammation in a mouse model of Parkinson's disease.

Chukai Yusaku Y Arisumi Konatsu K Yasunaga Genta G Sakai Hiroki H Tatara Yota Y Kasai Shuya S Yamashita Tetsuro T Ishiyama Eri E Kiyokawa Kokoro K Ozaki Taku T

Biochimica et biophysica acta. General subjects 20260416 7

Carnosine, an imidazole dipeptide, has potential for treating neurodegenerative diseases, including Parkinson's disease. However, carnosine-degrading enzymes limit its bioavailability. In this study, we established a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced Parkinson's disease and intranasally administered balenine, a carnosine analog featuring a methylated imidazole that is resistant to degradation enzymes, to target the brain via the olfactory ep ...[more]

PMID: 41999927

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Project description:The full complement of molecular pathways contributing to Parkinson’s disease (PD) pathogenesis remains unknown. Here, to address this issue, we began by using a high-resolution variant of functional magnetic resonance imaging (fMRI) to pinpoint brainstem regions differentially affected by, and resistant to, the disease. Then, relying on the imaging information as a guide, we profiled gene expression levels of postmortem brain samples and used a factorial statistical model to identify a disease related decrease in the expression of the polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a series of studies were performed to confirm the pathogenic relevance of this finding. First, to test for a causal link between polyamines and α-synuclein toxicity, we investigated a yeast model expressing α-synuclein. Polyamines were found to enhance the toxicity of α-synuclein, and an unbiased genome-wide screen for modifiers of α-synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology we investigated a mouse model expressing α-synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, while Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, we genotyped PD patients and controls and isolated a rare but novel variant in the SAT1 gene, although the functional significance of this genetic variant was not identified. Taken together, the results suggest that the polyamine pathway contributes to PD pathogenesis. Imaging-guided microarray In principle, gene expression profiling techniques like microarray are well suited to identify molecular pathways contributing to the pathogenesis of complex diseases. In practice, however, microarray applied to diseases of the brain present a number of analytic challenges. By identifying regions within the same brain structure that are differentially targeted by and resistant to a disease, imaging-guided microarray is an approach designed to address these limitations. Specifically, guided by the spatial information generated from high resolution functional imaging, a 2x2 factorial analysis-of-variance can be designed, including both within and between group factors, and this “double subtraction” model is effective in improving signal-to-noise in a microarray experiment. Relying on imaging findings, we harvested the DMNV from 6 postmortem brains with evidence of PD and from 5 control brains. The postmortem PD cases were evaluated for pathological changes (Lewy body-containing neurons and Lewy neurites evidenced with antibodies directed against α-synuclein aggregates) that matched the pattern proposed by Braak. We relied on the imaging results to identify a neighboring medullary region relatively unaffected by the disease to be used as a within-brain control. We decided on the inferior olivary nucleus (ION), because it is histologically identifiable, and harvested the ION from each of the 6 PD cases and 5 controls. Microarray techniques were used to generate gene expression profiles for each of the 22 tissue samples. A repeated-measures 2x2 factorial ANOVA model constructed for the imaging study was applied to the expression dataset, in which expression levels from two regions of the medulla (DMNV vs. ION) were included as the first within group factor, diagnosis (PD vs. controls) was the between group factor, and age and sex were included as covariates. Based on current literature, one of the top hits (SAT1) was investigated further to determine if it played a role in PD pathogenesis.