Jun 13, 2024 · Scientists have developed α-synuclein PET tracers, but they have limitations (Aug 2023 conference news). One, called F0502B, poorly slipped into the brains of rhesus macaques, while Merck's MK-7337 had off-target binding in monkey cerebella. AC Immune’s ACI-12589 detects α-synuclein aggregates in MSA, but not those in PD, which are much ...

Jul 3, 2002 · The transgene consists of the human α-synuclein sequence with the A53T mutation driven by the mouse prion protein (PrP) promoter. The transgene inserted at Chr10:95350683-95399000 (Build GRCm38/mm10), causing a 249 Kb deletion that disrupted the 2310039L15Rik gene, which codes for a lincRNA (Goodwin et al., 2017). Phenotype Characterization

Sep 20, 2024 · No inclusions formed when neurons did not express α-synuclein (middle). [Courtesy of Lam et al., Neuron, 2024.] In neurons expressing a piggyBac A53T-α-synuclein transgene the scientists found two different types of aggregate (image below). Type I inclusions contained a lipid-rich mix of vesicular structures and mitochondrial membranes, but ...

Mar 22, 2017 · Behaviorally, α-synuclein KO mice appear largely normal. They display normal reflexes and sensory abilities. They performed similarly to controls in most assays of motor function (e.g., Rotarod, distance travelled in open-field test); however, they reared on hind legs less frequently than wild-type controls.

Bellucci noted that α-synuclein loiters in pre-synapses, putting it in the right place to bind synaptic proteins, and that its presence there correlates with neurodegeneration (Schulz-Schaeffer, 2010). She previously reported that α-synuclein interacts with synapsin III in nerve terminals to regulate dopamine release (Zaltieri et al., 2015).

Jun 12, 2022 · How α-synuclein affected these processes was unknown. To follow up, first author Erinc Hallacli expressed α-synuclein in a yeast model system containing tagged RNA-binding proteins that acted as reporters. α-Synuclein affected the function of several RBPs, particularly those that regulated mRNA degradation.

Mar 27, 2022 · Mark Cookson National Institute on Aging; Posted: 29 Mar 2022 Finding ways to image α-synuclein pathology in the human brain is a critical need in the neurodegenerative field, as this could allow for both evaluation of disease progression and, potentially, for differential diagnosis between diseases.

Mutant human α-synuclein was detected in dopaminergic neurons, both cytoplasmic and nuclear. Lewy body-like inclusions are not observed in this model, at least by four months of age. Compared with non-transgenic littermates, HM2 mice exhibit an age-dependent decrease in striatal dopamine and its primary metabolites, homovanillic acid (HVA) and ...

Mar 22, 2017 · Neurons in the enteric nervous system of the gut develop α-synuclein pathology, but neurons in the brain are spared and there is no evidence of dopaminergic neuron loss (Kuo et al., 2010). Homozygous mice have four copies of the human transgene (two on chromosome 3 and two on chromosome 14) and robust expression in the brain and colon.

Feb 9, 2024 · For now, this means α-synuclein seeds that can be amplified from the CSF, but other assays might be added as they become validated. Carriers of fully penetrant SNCA mutations are the lone exception to the requirement for a positive α-synuclein seeding test. This is because these rare mutations invariably spark neuronal α-synuclein aggregation.