Drosophila Models of Parkinson's Disease: Discovering Relevant Pathways and Novel Therapeutic Strategies

Figure 1

Representative phenotypes found in different Drosophila PD models. (a)–(d) DA neuron loss detected in Drosophila adult brains by immunostainings with anti-TH antibody, which specifically recognizes these neurons, in paraffin sections (a, b) or whole-mount brains (c, d). A reduction in the number of DA neurons is observed in both Ddc-GAL4/DJ-1α RNAi (b) [50] and Ddc-GAL4/UAS-α-Synuclein (d) [51] brains when compared to age-matched Ddc-GAL4/+ controls (a, c). (e)–(j) Examples of phenotypes observed in parkin LOF mutants (f, h, j) compared to controls (e, g, i). They include downturned wings (f), muscle degeneration (h), and abnormal mitochondrial morphology (j) [52]. (k) Premature loss of climbing ability in transgenic flies expressing wild-type, A30P, and A53T mutant forms of α-Synuclein [34]. (l) Reduced lifespan of DJ-1β mutants compared to y, w control flies cultured under the same conditions. (m) Elevated sensitivity to paraquat stress in DJ-1αand DJ-1β mutant flies, represented by calculating the percentage of dead flies after feeding 15 mM for 18 h [53]. (n)–(o) Quantification of oxidative stress levels in 1-2-day-old DJ-1β mutants and age-matched y, w control flies. DJ-1β mutants show an increase in lipid peroxidation (LPO) product malondialdehyde (MDA) (n). Catalase (CAT) enzymatic activity is also increased (o) [54].