These findings support the hypothesis that direct irradiation of brain tissue may responsible for improved outcomes observed in stroke patients, although an indirect effect cannot be excluded. Since blood appreciably decreases the penetrance of light, it seems that direct effects observed may only require low levels of irradiance and low energy densities. Coupled with the ongoing research concerning photoabsorption, cytochrome C oxidase, and ATP generation, our findings provide a foundation for further investigation of the effects of near infrared light of the brain status post-stroke. Spinocerebellar ataxia type 3 or Machado-Joseph disease is the most frequent among the SCA subtypes, comprising about 21% of the worldwide cases of autosomal dominant cerebellar ataxias. In SCA3, the disease protein Ataxin-3 harbors an abnormally elongated polyQ expansion, causative for disease. Such elongated polyQ expansions are the common theme in various other disorders, the reason why these disorders are often summarized as polyQ diseases. The disease-linked proteins share no homology to each other apart from the polyQ tract, suggesting a common pathogenic mechanism leading to the development of disease. According to the toxic fragment hypothesis, the polyQ tract itself is the actual toxic BEZ235 species due to its ability to cause neurodegeneration. There is an inverse correlation between repeat number and age of onset. Additionally, severity of the disease increases with the length of the CAG tract. Expansion of the polyQ stretch in the disease protein renders the mutant variant prone to aggregation. The actual inclusions are formed through putative toxic intermediates. Nevertheless, the toxicity of the different aggregating species is still under discussion, favoring oligomers of the disease proteins as the trigger of neuronal dysfunction and eventually neurodegeneration. Additionally, nuclear translocation of proteolytically cleaved polyQ proteins and formation of nuclear inclusions are early events in pathogenesis and known to be hallmarks in polyQ diseases. Impairment of the ubiquitin-proteasomal system seems to be a key factor in polyQ pathogenesis. UPS activity is needed to clear aggregates of mutated proteins. Cells with impaired UPS therefore fail to attenuate the toxic effects of polyQ species. Besides misfolding of the mutant proteins and impaired cellular protein homeostasis, many other hypotheses have been proposed to explain polyQ disease pathogenesis. Among these are deleterious protein interactions, transcriptional dysregulation, mitochondrial dysfunction, impaired axonal transport, anomalous neuronal signaling and RNA toxicity. With regard to similar toxicity of heterogeneous proteins in different cellular and spatial settings, there is overwhelming need for insight into polyQ protein-interacting genes in order to decipher the processes involved in neurotoxicity. Drosophila has proven to be a valuable model organism in research of neurodegenerative diseases, not least in diverse screening approaches. Usage of the VDRC RNAi library allows large-scale, almost genome-wide screening. However, RNAi-mediated gene silencing approaches might cause off-target effects. Although the VDRC library was designed to limit off-target effects, we are aware that some of our candidates might result from off-target effects.