Folinic acid is neuroprotective in a fly model of Parkinson’s disease associated with pink1 mutations

Mutations in PTEN-induced kinase 1 (PINK1) cause autosomal recessive and early-onset Parkinson’s disease (PD). PINK1, a kinase involved in a mitochondrial quality control mechanism, acts by promoting the autophagic degradation of damaged mitochondria. Mutations in PINK1 lead to the accumulation of impaired mitochondria and the death of dopaminergic neurons. Folates act as single carbon donors in metabolic reactions such as nucleotide synthesis from purines. Oral folates are available in two forms, folic and folinic acid (FA and FiA, respectively). In Drosophila pink1 mutants, enhancing nucleotide biosynthesis via dietary supplementation with FA during development rescues mitochondrial function and leads to neuroprotection in adults. Orally available FiA bypasses the deconjugation and reduction steps required with FA and is more metabolically active. Here, we investigated the neuroprotective potential of dietary supplementation with FiA in adult pink1 mutant flies. We show that an FiA-enriched diet begun at early to middle stages of adulthood prevents the degeneration of dopaminergic neurons observed in pink1 mutants. An FiA-enriched diet might therefore delay or prevent the neuronal loss in patients with PINK1 mutations and may ameliorate other diseases linked to mitochondrial defects.