Ando, M., Okamoto, Y., Higuchi, Y., Yuan, J.H., Yoshimura, A., Yano, C., Nagatomo, R., Hobara, T., Kojima, F., Hiramatsu, Y., Nozuma, S., Sakiyama, Y., Takashima, H. (2026). Arginine ameliorates motor and survival deficits in MFN2-Deficient Drosophila models.  Neurotherapeutics 23(3): e00900.

FBrf0265573

Research paper

Charcot-Marie-Tooth disease type 2 A (CMT2A) is an inherited axonal neuropathy linked to mutations in MFN2, a key regulator of mitochondrial dynamics. Currently, no effective drug therapies exist. l-arginine has shown promise in treating mitochondrial disorders, though its effect on MFN2-associated neuropathy remains uncertain. To investigate this, we used Drosophila models with the neuron-specific knockdown of Marf, the fly ortholog of MFN2, employing a temporally controlled GAL4/UAS system. Flies were administered different doses of l-arginine to examine its influence on motor ability and lifespan. To evaluate responses under mitochondrial stress, flies were also treated with rotenone, a mitochondrial complex I inhibitor. l-arginine markedly improved climbing performance under baseline conditions and extended lifespan under both baseline and stress conditions. However under rotenone-induced mitochondrial stress, high-dose l-arginine improved survival without a corresponding improvement in locomotor performance. These results support a neuroprotective role for l-arginine in MFN2-deficient Drosophila, possibly through effects on mitochondrial dynamics involving complex I. l-arginine may hold therapeutic promise for CMT2A, meriting further investigation in vertebrate models.

PMC13084675 (PMC) (EuropePMC)