Can ‘Cryptic Peptides’ Identify People with TDP-43 Pathology?
Mis-splicing events produce novel proteins that can be detected in the cerebrospinal fluid of ALS/FTD patients before their symptoms even start.
NEWS
The Chaperone FKBP12 Shields Tau from Aggregation
The protein binds to segments of tau prone to aggregate, preventing neurofibrillary tangles and neurodegeneration.
Nothing to Sneeze At: Viruses Raise Risk of Neurodegenerative Disease
Twelve severe viral illnesses boosted risk up to 15 years after infection.
In Endosomes, SORL1 Dimerizes, Boosting Retromer Recycling of APP
SORL1 may form polymers that bind and stabilize the retromer, facilitating the recycling of APP and other substrates.
Not All Bad: Phosphorylated α-Synuclein Modulates Neurotransmission
p-S129syn better binds its synaptic vesicle protein partners than does plain α-synuclein.
In Nasu-Hakola Disease, DAP12-Deficient Microglia Kick Repair into Overdrive
The first study to survey the brain transcriptomes of people with NHD found microglia and astrocytes frantically repairing injury, and narrowing blood vessels.
Did Dementia Patient Care Go Downhill During the COVID Pandemic?
Data from six countries showed prescriptions for antipsychotic drugs rose in 2020, and remain high.
Droplets in the Bucket? Introducing en Masse Single-Synapse RNA-Seq
A new method reveals distinct synaptic states, some tied to amyloidosis, that were not seen in prior nuclear transcriptomic data.
SPOTLIGHT
Can “Cryptic Peptides” Identify People with TDP-43 Pathology?
The nuclear protein TDP-43 clumps in the cytosol in several neurodegenerative diseases—ALS, FTD, LATE-NC—but scientists have had no way to detect this pathology in living people. Until now. Two studies have found that mis-spliced transcripts, which accumulate in the absence of nuclear TDP-43, are sometimes made into proteins with new domains. Such “cryptic peptides” appear in the cerebrospinal fluid of ALS/FTD patients, rising before symptoms even develop. The findings kindle hope for new diagnostic and prognostic markers of TDP-43 proteopathies.
The Chaperone FKBP12 Shields Tau from Aggregation
The chaperone protein FKBP12 interacts with tau to attenuate aggregation. But how it did so was unclear—until now. FKBP12 binds to two specific motifs in tau that are aggregation-prone when phosphorylated. Overexpressing the chaperone protein prevented neurofibrillary tangles from forming in cultured neurons and quelled neurodegeneration in three-dimensional cultures of human neurons and astrocytes.
Strings of SORL1?
SORL1 is a top AD risk gene, and the protein it encodes is responsible for whisking other proteins, including APP, out of the endosome. A new study illuminates what could be a key mechanism involved in the process. SORL1 dimerizes on the endosomal membrane, and this pairing appears critical for endosomal recycling. It may even form polymers.
Not All Bad: Phosphorylated α-Synuclein Modulates Neurotransmission
Lewy bodies accumulate α-synuclein phosphorylated at serine 129, but does this modified synuclein have a physiological function? Yes, according to two recent studies. Both claim that neural activity sparks S129 phosphorylation. One shows that this modification facilitates α-synuclein binding to synaptic vesicle proteins; the other that p-S129syn enhances neurotransmission. Mice living in an enriched environment make more p-S129syn than jaded controls and muster stronger synaptic plasticity.
Nasu-Hakola Transcriptomics
Homozygous mutations in TREM2 or its adaptor, DAP12, lead to an early onset dementia known as Nasu-Hakola disease. The first study to analyze cellular transcriptomes of people with the disease found that glia are intensely engaged in tissue repair and wound healing, while oligodendrocytes stop producing myelin, the vasculature shrinks, and neurons fade. Counterintuitively, the skew toward repair may ultimately contribute to the damage, scientists proposed.
Join The Conversation
Professional Resources
New in last 7 days
-
Grants
- New Items: 6
- Total Items: 575
-
Jobs
- New Items: 3
- Total Items: 62
-
Conference Calendar
- New Items: 4
- Total Items: 81
- Member Directory
Latest Comments