Chronic blue light leads to accelerated aging in Drosophila by impairing energy metabolism and neurotransmitter levels.

Blue light (BL) is becoming increasingly prevalent in artificial illumination, raising concerns about its potential health hazard to humans. In fact, there is evidence suggesting that acute BL exposure may lead to oxidative stress and death of retinal cells specialized for photoreception. On the other hand, recent studies in demonstrated that chronic BL exposure across lifespan leads to accelerated aging manifested in reduced lifespan and brain neurodegeneration even in flies with genetically ablated eyes, suggesting that BL can damage cells and tissues not specialized for light perception.

Age-dependent effects of blue light exposure on lifespan, neurodegeneration, and mitochondria physiology in Drosophila melanogaster.

Blue light is a predominant component of light emitting devices (LEDs), which are increasingly present in our environment. There is already accumulating evidence that blue light exposure causes damage to retinal cells in vitro and in vivo; however, much less is known about potential effects of blue light on non-retinal cells. That blue light may be detrimental at the organismal level independent from retinal effect was recently shown by findings that it reduces lifespan in worms and also in flies with genetically ablated retinas.

FTD-associated mutations in Tau result in a combination of dominant and recessive phenotypes.

Although mutations in the microtubules-associated protein Tau have long been connected with several neurodegenerative diseases, the underlying molecular mechanisms causing these tauopathies are still not fully understood. Studies in various models suggested that dominant gain-of-function effects underlie the pathogenicity of these mutants; however, there is also evidence that the loss of normal physiological functions of Tau plays a role in tauopathies. Previous studies on Tau in Drosophila involved expressing the human Tau protein in the background of the endogenous Tau gene in addition to inducing high expression levels.

Disease-Associated Mutant Tau Prevents Circadian Changes in the Cytoskeleton of Central Pacemaker Neurons.

A hallmark feature of Alzheimer's disease (AD) and other Tauopathies, like Frontotemporal Dementia with Parkinsonism linked to chromosome 17 (FTDP-17), is the accumulation of neurofibrillary tangles composed of the microtubule-associated protein Tau. As in AD, symptoms of FTDP-17 include cognitive decline, neuronal degeneration, and disruptions of sleep patterns. However, mechanisms by which Tau may lead to these disturbances in sleep and activity patterns are unknown.

Disease-Associated PNPLA6 Mutations Maintain Partial Functions When Analyzed in .

Mutations in patatin-like phospholipase domain-containing protein 6 (PNPLA6) have been linked with a number of inherited diseases with clinical symptoms that include spastic paraplegia, ataxia, and chorioretinal dystrophy. PNPLA6 is an evolutionary conserved protein whose ortholog in is Swiss-Cheese (SWS). Both proteins are phospholipases hydrolyzing lysophosphatidylcholine (LPC) and phosphatidylcholine (PC).

Daily blue-light exposure shortens lifespan and causes brain neurodegeneration in .

Light is necessary for life, but prolonged exposure to artificial light is a matter of increasing health concern. Humans are exposed to increased amounts of light in the blue spectrum produced by light-emitting diodes (LEDs), which can interfere with normal sleep cycles. The LED technologies are relatively new; therefore, the long-term effects of exposure to blue light across the lifespan are not understood.

ER responses play a key role in Swiss-Cheese/Neuropathy Target Esterase-associated neurodegeneration.

Swiss Cheese (SWS) is the Drosophila orthologue of Neuropathy Target Esterase (NTE), a phospholipase that when mutated has been shown to cause a spectrum of disorders in humans that range from intellectual disabilities to ataxia. Loss of SWS in Drosophila also causes locomotion deficits, age-dependent neurodegeneration, and an increase in lysophosphatidylcholine (LPC) and phosphatidylcholine (PC). SWS is localized to the Endoplasmic Reticulum (ER), and recently, it has been shown that perturbing the membrane lipid composition of the ER can lead to the activation of ER stress responses through the inhibition of the Sarco/Endoplasmic Reticulum Ca ATPase (SERCA).

Deletion of a specific exon in the voltage-gated calcium channel gene disrupts locomotion in larvae.

TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein that regulates transcription, translation and alternative splicing of mRNA. We have shown previously that null mutations of the ortholog, (), causes severe locomotion defects in larvae that are mediated by a reduction in the expression of a type II voltage-gated calcium channel, (). We also showed that TDP-43 regulates the inclusion of alternatively spliced exons of ; mutants showed significantly increased expression of isoforms lacking exon 7, a particularly notable finding as only one out of the 15 predicted isoforms lacks exon 7.