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Updated: Jul 2, 2025
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Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
Published on: January 5, 2016
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FABP2 is Involved in Intestinal α-Synuclein Pathologies
Tomoki Sekimori1, Kohji Fukunaga1, Hideki Oizumi2
1Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 980-8578 Sendai, Japan.
Journal of Integrative Neuroscience
|February 29, 2024
Summary
Intestinal fatty acid-binding protein (FABP2) may facilitate the gut-to-brain spread of alpha-synuclein, a key factor in synucleinopathies like Parkinson's disease. FABP2 levels correlate with disease progression, suggesting its role in pathogenesis.
Area of Science:
- Neuroscience
- Gastroenterology
- Molecular Biology
Background:
- The gut-to-brain propagation of pathological alpha-synuclein is a leading hypothesis in synucleinopathy pathogenesis.
- The precise mechanisms underlying this gut-to-brain pathway remain largely unknown.
- Intestinal fatty acid-binding protein 2 (FABP2) is a gut-localized protein implicated in this process.
Purpose of the Study:
- To investigate the role of FABP2 in the uptake of alpha-synuclein into enteric neurons.
- To clarify the pathological significance of FABP2 in synucleinopathy development and progression.
- To explore FABP2 as a potential biomarker for synucleinopathy progression.
Main Methods:
- Primary cultured enteric neurons from mouse small intestinal myenteric plexus were used to study alpha-synuclein uptake in relation to FABP2.
- Plasma concentrations of disease-related proteins were quantified in patients with synucleinopathies.
- The correlation between plasma FABP2 levels and disease progression was analyzed.
Main Results:
- Alpha-synuclein uptake into enteric neurons was found to co-localize with FABP2.
- Plasma FABP2 and alpha-synuclein levels in Parkinson's disease patients varied with disease duration.
- The FABP2/alpha-synuclein ratio demonstrated higher discriminant ability for early Parkinson's disease detection compared to individual markers.
Conclusions:
- FABP2 appears to play a role in the pathogenesis and progression of alpha-synucleinopathies.
- FABP2 is a significant molecule for understanding the mechanisms linking prodromal synucleinopathy to disease onset and advancement.
- FABP2 may serve as a potential therapeutic target or diagnostic marker for synucleinopathies.
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