Long somatic DNA-repeat expansion drives neurodegeneration in Huntington's disease.

In Huntington's disease (HD), striatal projection neurons (SPNs) degenerate during midlife; the core biological question involves how the disease-causing DNA repeat (CAG) in the huntingtin (HTT) gene leads to neurodegeneration after decades of biological latency. We developed a single-cell method for measuring this repeat's length alongside genome-wide RNA expression. We found that the HTT CAG repeat expands somatically from 40-45 to 100-500+ CAGs in SPNs.

Early developmental changes in GABAA receptor expression in nucleus accumbens medium spiny neurons.

The expression of GABARs goes through large scale, evolutionarily conserved changes through the early postnatal period. While these changes have been well-studied in brain regions such as the hippocampus and sensory cortices, less is known about early developmental changes in other brain areas. The nucleus accumbens (NAc) is a major hub in the circuitry that mediates motivated behaviors and disruptions in NAc activity is a part of the neuropathology observed in mood and substance use disorders.

SKA2 enhances stress-related glucocorticoid receptor signaling through FKBP4-FKBP5 interactions in neurons.

Genes involved in regulating the hypothalamic-pituitary-adrenal (HPA) axis, including the glucocorticoid receptor (GR), are linked to various stress-related psychopathologies including bipolar disorder as well as other mood and trauma-related disorders. The protein product of the cell cycle gene, is a GR interaction partner in peripheral cells. However, the precise roles of SKA2 in stress and GR signaling in the brain, specifically in nonreplicating postmitotic neurons, and its involvement in HPA axis regulation remain unclear.

Dementia with lewy bodies patients with high tau levels display unique proteome profiles.

Background: Clinical studies have long observed that neurodegenerative disorders display a range of symptoms and pathological features and, in some cases, overlap, suggesting that these diseases exist on a spectrum. Dementia with Lewy Bodies (DLB), a synucleinopathy, is a prominent example, where symptomatic similarities with tauopathy, Alzheimer's disease, are observed. Although tau pathology has been observed in DLB, the interplay between tau and α-synuclein is poorly understood at a molecular level.