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Neurodegenerative disorders such as Alzheimer's or Parkinson's disease place an enormous burden on patients, their relatives, and society as a whole. Modifying the activity of specific proteins by use of pharmaceutical compounds can combat neurodegeneration. However, the proteins that should be targeted to best achieve this effect are unknown. I posit that a strong basis for identifying the most relevant targets can be created by Darwinian selection of adaptive mutations, during accelerated evolution in Drosophila (fruit flies). 

For example, Parkinson's disease can be modelled in flies by expressing alpha-synuclein, which promotes neurodegeneration in humans. Over many generations, a population of such flies will accumulate adaptive (beneficial) mutations that specifically compensate for the detrimental effect of toxic stress caused by alpha-synuclein. Hence, the proteins encoded by the genes subjected to these adaptive mutationes will be interesting potential drug targets. 

Like in humans, neurodegenerative changes are exacerbated by aging in the Drosophila models, and an aging period is often implemented when studying them. This increases the "effective" generation time, which, together with the many generations needed for sufficient adaptation to occur, would require a total experimental period too long to be practical. However, a simple genetic method to increase the mutation rate ten times has recently been introduced in Drosophila, which mitigates this concern by accelerating the evolutionary process. 

Whole-genome sequencing of the adapted flies, compared to first-generation controls and flies living through the same number of generations but not exposed to toxic stress, will be used to map the adaptive genotypes that harbor the beneficial mutations. The experiment will be repeated with several cohorts evolving in parallel, with the idea that genes consistently mutated across cohorts will be particularly intriguing candidates for further analysis.