Impaired RNA Binding Does Not Prevent Histone Modification Changes in a FUS ALS/FTD Yeast Model.

Mutations in the RNA-binding protein FUS are linked to amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). FUS mutants mislocalize and aggregate in dying neurons. We previously established that FUS proteinopathy is linked to changes in the histone modification landscape in a yeast ALS/FTD model.

[PRION] States Are Associated with Specific Histone H3 Post-Translational Modification Changes.

Prions are proteins able to take on alternative conformations and propagate them in a self-templating process. In , prions enable heritable responses to environmental conditions through bet-hedging mechanisms. Hence, [PRION] states may serve as an atypical form of epigenetic control, producing heritable phenotypic change via protein folding.

Epidrugs in Amyotrophic Lateral Sclerosis/Frontotemporal Dementia: Contextualizing a Role for Histone Kinase Inhibition in Neurodegenerative Disease.

Breakthroughs in understanding the epigenetic mechanisms involved in neurodegenerative disease have highlighted "epidrugs" as a potential avenue for therapeutic development. Here, we expand on the future of epidrugs against neurodegeneration and discuss promising novel targets underexploited thus far: histone kinases.

Trichostatin A Relieves Growth Suppression and Restores Histone Acetylation at Specific Sites in a FUS ALS/FTD Yeast Model.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that often occurs concurrently with frontotemporal dementia (FTD), another disorder involving progressive neuronal loss. ALS and FTD form a neurodegenerative continuum and share pathological and genetic features. Mutations in a multitude of genes have been linked to ALS/FTD, including The FUS protein aggregates and forms inclusions within affected neurons.

Changes in Histone H3 Acetylation on Lysine 9 Accompany Aβ 1-40 Overexpression in an Alzheimer's Disease Yeast Model.

Alzheimer's Disease (AD), the most common type of dementia, is a neurodegenerative disease characterized by plaques of amyloid-beta (Aβ) peptides found in the cerebral cortex of the brain. The pathological mechanism by which Aβ aggregation leads to neurodegeneration remains unknown. Interestingly, genetic mutations do not explain most AD cases suggesting that other mechanisms are at play.

Investigation of the Effects and Mechanisms of Anticancer Action of a Ru(II)-Arene Iminophosphorane Compound in Triple Negative Breast Cancer Cells.

Triple negative breast cancer (TNBC) is one of the breast cancers with poorer prognosis and survival rates. TNBC has a disproportionally high incidence and mortality in women of African descent. We report on the evaluation of Ru-IM (1), a water-soluble organometallic ruthenium compound, in TNBC cell lines derived from patients of European (MDA-MB-231) and African (HCC-1806) ancestry (including IC values, cellular and organelle uptake, cell death pathways, cell cycle, effects on migration, invasion, and angiogenesis, a preliminary proteomic analysis, and an NCI 60 cell-line panel screen).

Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models.

Neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), cause the loss of hundreds of thousands of lives each year. Effective treatment options able to halt disease progression are lacking. Despite the extensive sequencing efforts in large patient populations, the majority of ALS and PD cases remain unexplained by genetic mutations alone.

Epigenetics in amyotrophic lateral sclerosis: a role for histone post-translational modifications in neurodegenerative disease.

Amyotrophic lateral sclerosis (ALS) is the third most common adult onset neurodegenerative disorder worldwide. It is generally characterized by progressive paralysis starting at the limbs ultimately leading to death caused by respiratory failure. There is no cure and current treatments fail to slow the progression of the disease.

The impact of histone post-translational modifications in neurodegenerative diseases.

Every year, neurodegenerative disorders take more than 5000 lives in the US alone. Cures have not yet been found for many of the multitude of neuropathies. The majority of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson's disease (PD) cases have no known genetic basis.