When researchers directly convert skin cells into neurons, skipping the stem-cell step, the cells express gene signatures that reflect the age of their donors.
Knocking out interferon-β in mice caused α-synuclein to pile up in neurons, leading to neurodegeneration with features of Parkinson’s disease.
Microglia may transport tau between neurons by taking it up and secreting it in exosomal packages. Blocking exosome synthesis stopped the transfer.
Granules in the nucleus and cytoplasm may owe their genesis and shape to liquefied forms of ALS-linked proteins, such as FUS and hnRNPA1.
Researchers report the first known enzyme that combines disaggregase and protease activity.
A CD33 variant associated with Alzheimer’s boosts levels of wild-type TREM2, hinting that these risk factors could share a common mechanism.
The genetic relics of ancient, dormant retroviruses pepper the human genome. One such virus reanimates in about one-third of ALS cases.
Analysis of the avagacestat trial of 2012 details the side effects that sank the drug, and the outcomes that support CSF biomarkers for prodromal Alzheimer’s disease.
The 1000 Genomes consortium released its final report and sequence data set. It will help scientists studying neurodegenerative diseases better interpret GWAS findings.
Acetylated tau accumulates in Alzheimer’s disease, and associates with pathology and behavioral measures in mouse models.
Drosophila were just fine, thank you very much, despite carrying the ALS- and FTD-linked repeats in the same intronic context as they occur in people.
In a large population study, middle-aged people who developed atrial fibrillation were about twice as likely as their peers to succumb to dementia over the next 20 years.
Fresh neurons from a human brain are not easy to come by, so researchers generate neurons from skin cells instead. This transformation often involves a pit stop as a pluripotent stem cell, which erases vestiges of the donor’s age. Researchers now report that when skin cells are directly converted into neurons instead, the resulting cells retain an age-specific gene expression signature. The researchers identified RanBP17, a protein involved in keeping the nucleus and cytoplasm separate, as a master regulator of aging in both neurons and fibroblasts. The conversion technique could offer insights into the influence of aging factors on neurodegenerative disease.
Dead and dying neurons can promote inflammatory responses in the brain, but could changes in immune signaling actually cause cells to degenerate? That’s what researchers suggest in this week’s Cell. Loss of the anti-inflammatory cytokine IFN-β crippled the ability of mouse neurons to dispose of unwanted proteins through autophagy. Harmful proteins such as α-synuclein built up, and the animals developed a neurodegenerative condition that shares some features with Parkinson’s disease and dementia with Lewy bodies.
Abnormal protein aggregation is common to neurodegenerative diseases—but what if aggregation were a consequence of normal organelle formation taken to the extreme? Defining a new area of research, scientists are realizing that certain proteins condense into liquid droplets within the cell, lending a modicum of structure to transient, membrane-free organelles such as stress granules. While this newly appreciated feat of cellular biophysics may serve a physiological purpose, it also puts proteins at risk of condensing even further, into the solid fibrils seen in neurodegeneration. This could be important in ALS and beyond. Learn about this emerging disease hypothesis from Simon Alberti, Cliff Brangwynne, Nicolas Fawzi, and Paul Taylor, who will present recent findings in an Alzforum Webinar on October 30.
To get rid of protein aggregates, cells must first break up the clumps, then digest the individual pieces. Now researchers have identified the first known enzyme that can do both. HTRA1 is known to be a serine protease, but it can also weakly tease apart tangled tau strands. With some engineering to optimize this activity, the protein might make a promising candidate to bust up deposits, researchers said.
Some Alzheimer’s risk genes may be partners in crime, influencing each other’s expression or behavior. In this week’s Nature Neuroscience, researchers report immune-related AD risk genes interact in human monocytes. Of particular note, increased expression of the CD33 receptor boosted the amount of wild-type TREM2 on the cell surface, suggesting a functional connection between these proteins.
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