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Updated: May 28, 2026
Mass Histology to Quantify Neurodegeneration in Drosophila
Published on: December 15, 2016
5-ALA/SFC Mitigates Tau Toxicity via Lowering Oxidative Stress in a Drosophila Model of Tau Toxicity
Arisa Tamura1, Marie Noguchi1, Naoko Nozawa2
1Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
Abstract:
Mitochondrial dysfunctions contribute to the pathogenesis of tauopathies, a group of neurodegenerative diseases with abnormal accumulation of microtubule-associated protein tau. The combination of 5-aminolevulinic acid (5-ALA) and sodium ferrous citrate (SFC) is known to improve mitochondrial functions. Here, we report that 5-ALA combined with SFC (5-ALA/SFC) improves mitochondrial functions and mitigates neurodegeneration in transgenic Drosophila expressing human tau. We found that tau reduces ATP levels, decreases mitochondrial distribution to neurites, and increases mitochondrial reactive oxygen species (ROS). Expression of oxidative phosphorylation (OXPHOS) genes was upregulated, and activities of complexes I and IV were elevated. Feeding 5-ALA/SFC to tau flies lowers oxidative damage without correcting OXPHOS activities or mitochondrial distribution. 5-ALA/SFC treatment suppressed pathological tau phosphorylation and mitigated tau-induced neurodegeneration. These results suggest that 5-ALA/SFC attenuates a neurodegenerative pathway involving tau, mitochondria, and ROS.
Insights
5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) improves mitochondrial function and reduces neurodegeneration in tauopathy models. This combination therapy shows potential for treating neurodegenerative diseases linked to tau pathology and mitochondrial dysfunction.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Genetics
Background:
- Mitochondrial dysfunction is implicated in tauopathies, neurodegenerative diseases characterized by abnormal tau protein accumulation.
- 5-aminolevulinic acid (5-ALA) combined with sodium ferrous citrate (SFC) is known to enhance mitochondrial functions.
Purpose of the Study:
- To investigate the therapeutic potential of 5-ALA/SFC in mitigating tau-induced neurodegeneration.
- To elucidate the effects of 5-ALA/SFC on mitochondrial function and oxidative stress in a tauopathy model.
Main Methods:
- Utilized transgenic *Drosophila* models expressing human tau.
- Administered 5-ALA/SFC orally to assess its impact on mitochondrial parameters, oxidative damage, tau phosphorylation, and neurodegeneration.
Main Results:
- Tau expression led to reduced ATP levels, impaired mitochondrial distribution, and increased reactive oxygen species (ROS).
- 5-ALA/SFC treatment decreased oxidative damage and suppressed pathological tau phosphorylation.
- Neurodegeneration was mitigated in tau flies treated with 5-ALA/SFC, despite no correction in oxidative phosphorylation (OXPHOS) activities or mitochondrial distribution.
Conclusions:
- 5-ALA/SFC effectively attenuates tau-induced neurodegeneration by targeting a pathway involving tau, mitochondria, and ROS.
- This combination therapy presents a promising strategy for tauopathies and related neurodegenerative conditions.
