The protein FUS forms liquid organelles in healthy cells. Does it trigger neurodegeneration by switching to a solid state?
Appoptosin, a gene linked to progressive supranuclear palsy, triggers tauopathy by activating caspase-3, which cleaves tau to unleash its synaptotoxic potential.
For every unit increase in body mass index in midlife, the age at onset of AD dropped by more than half a year. Amyloid PET links the effect to AD pathology.
At AAIC, researchers reported that estrogen may decrease dementia risk if given to healthy women during early menopause.
Relieving systemic immune suppression facilitates the entry of immune cells into the brain and slows amyloid accumulation in a mouse model of aggressive Aβ pathology, scientists claim.
Scientists flesh out how PINK1 and parkin instigate mitophagy and what role the ALS genes optineuron and TBK1 play in the process.
A third trial continues in the United States
The fragment occurs naturally and rises after BACE inhibition, adding another layer of complexity to inhibitor therapy.
The ALS-linked protein FUS can undergo phase changes akin to a gas condensing into liquid and then solid, according to a paper in Cell. The liquid form is physiological, and it structures membraneless organelles such as stress granules, the scientists propose. The solid phase tends to be dangerous because FUS in this state aggregates. Might other proteins implicated in neurodegeneration do the same?
A pro-apoptotic gene elevated in people with progressive supranuclear palsy and other neurodegenerative diseases derails neurons. Alas, it does so not through the classical cell death pathway, but instead by promoting tauopathy. Researchers report that appoptosin activates caspase-3, which then snips tau. The resulting tau fragment forms aggregates and retreats to the synapses, where it causes damage and movement problems in mice. The researchers propose that this caspase-centric mechanism underlies many tauopathies, including perhaps Alzheimer’s disease and frontotemporal dementia.
A new study has tipped the scales in favor of the idea that midlife obesity has cognitive consequences later in life. Researchers reported that for every unit increment in body mass index at age 50, Alzheimer’s disease comes nearly seven months earlier. This hastening occurred independently of cardiovascular risk factors, and was also associated with the severity of tangles and plaques. Researchers saw the data as another sign that good health in midlife bears fruit in old age.
A leading experimental strategy for combating Alzheimer’s suppresses production of amyloid-β, but new data complicates the science behind this approach. Researchers have now identified an alternative, eta(η)-secretase cleavage of amyloid precursor protein. It generates longer, more abundant peptides than Aβ40/42. One η fragment suppresses synaptic plasticity. Levels of this species rise after β-secretase inhibition, raising the question of whether BACE inhibitor treatment could trade one toxic fragment for another. The jury is out on what the new APP cleavage means, if anything, for BACE inhibitor trials.
Hexanucleotide repeats in the C9ORF72 gene cause amyotrophic lateral sclerosis and frontotemporal dementia—but how? Three research groups now offer the same answer: The mutation disrupts RNAs exiting the nucleus, and proteins trying to get in. Different manifestations of the repeats may be responsible for the traffic jam. Some findings indicated the repeat-laden transcript are to blame, while others point the finger at polydipeptides translated from those RNAs. Experts agreed the real answer may be a bit of both.
- Benjamin Wolozin on ALS Protein Said to Liquefy, Then Freeze en Route to Disease
- Guenter Hoeglinger and Ulrich Müller on Killer Cleavage: Appoptosin Stokes Tauopathy through Caspase 3
- Santiago Rivera on Enter Aη: Alternative APP Cleavage Creates Synaptotoxic Peptide
- Laura Baker on Neither Exercise Nor Supplements Boost Cognition in Two Large Studies
- Johnathan Cooper-Knock on ALS Gene Repeats Obstruct Traffic Between Nucleus and Cytoplasm
- Robert Baloh on Study Suggests Respiratory Pacemaker Reduces ALS Survival
- Frédéric Checler on Enter Aη: Alternative APP Cleavage Creates Synaptotoxic Peptide