Biology subjects

Wert, K. J.

Publications and source records attributed to Wert, K. J..

2 recordsLinked to original sources

bioRxiv2024

Female sex hormones exacerbate retinal neurodegeneration

Neurodegenerative disorders such as Alzheimers disease and macular degeneration represent major sources of human suffering, yet the factors influencing disease severity remain poorly understood. Sex has been implicated as one potential modifying factor. Here, we show that female sex is a risk factor for worsened outcomes in a model of retinal degeneration. Further, we show that this susceptibility is caused by the presence of female-specific circulating sex hormones. The adverse effect of female sex hormones was specific to diseased retinal neurons, and depletion of these hormones ameliorated this phenotypic effect. These findings provide novel insights into the pathogenesis of neurogenerative diseases and how sex hormones can impact the severity of disease. These findings have far-reaching implications for clinical trial design and the use of hormonal therapy in females with certain neurogenerative disorders.

neuroscience↗

bioRxiv2023

Visual impairment cell non-autonomously dysregulates brain-wide proteostasis.

Loss of hearing or vision has been identified as a significant risk factor for dementia but underlying molecular mechanisms are unknown. In different Drosophila models of blindness, we observe non-autonomous induction of stress granules in the brain and their reversal upon restoration of vision. Stress granules include cytosolic condensates of p62, ATF4 and XRP1. This cytosolic restraint of the ATF4 and XRP1 transcription factors dampens expression of their downstream targets during cellular stress. Cytosolic condensates of p62 and ATF4 were also evident in the thalamus and hippocampus of mouse models of congenital or degenerative blindness. These data indicate conservation of the link between loss of sensory input and dysregulation of stress responses critical for protein quality control in the brain. One-sentence summaryDrosophila and mouse models link loss of visual input to dysregulated stress responses of neurons and glia in the brain.

neuroscience↗