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Tau P301S (Line PS19) - ALZFORUM This widely used tauopathy model was developed at the University of Pennsylvania School of Medicine by Virginia Lee, John Trojanowski, and colleagues As first reported in 2007 on a mixed background, PS19 mice develop neuronal loss and brain atrophy by eight months, principally in the hippocampus
Risvodetinib | ALZFORUM The rationale is based on the finding that activated Abl kinase contributes to pathogenesis by phosphorylating α-synuclein and promoting its aggregation and toxicity, and by inhibiting neuroprotective effects of the parkin protein (e g , Ko et al , 2010)
Pretty in PINK1, Cryo-EM Reveals How Kinase Anchors to Mitochondria From this perch, PINK1’s kinase domain springs into action, phosphorylating ubiquitin, which recruits the ubiquitin ligase Parkin—another PD-linked protein—to tag mitochondria for degradation While the broad strokes of this process are well-known, precisely how PINK1 remains anchored to the membranes of ailing mitochondria was a puzzle
Parkinsons Disease Research Models | ALZFORUM Progress in Parkinson's disease research and therapeutic development depends on robust preclinical models, including rodent models By organizing information related to the characterization of selected PD models, this resource conveys what is known about each one and facilitates comparison of phenotypes This resource was created in collaboration with The Michael J Fox Foundation (MJFF) to
Vodobatinib - ALZFORUM The rationale is based on the finding that activated Abl kinase contributes to pathogenesis by phosphorylating α-synuclein and promoting its aggregation and toxicity, and by inhibiting neuroprotective effects of the parkin protein (e g , Ko et al , 2010)
PINK1 Can Act Alone to Destroy Mitochondria, But Parkin Helps Adding parkin raised the proportion of cells to nearly 24 percent Thus, PINK1 can work alone, but parkin adds a big boost Youle and colleagues suspected that OPTN and NDP52 would work by recruiting LC3, but they were surprised The mitochondria of double mutants missing both autophagy receptors still collected some LC3, but pentaKOs did not
A Biological Definition of Parkinson’s Disease: Two . . . - ALZFORUM These Lewy-less, biomarker-negative PD cases include most homozygous carriers of pathogenic mutations in the Parkin (PRKN) gene, and a proportion of LRRK2 mutation carriers The authors propose categorizing these cases as α-synuclein-negative (S-) forms of PD
Dopamine covalently modifies and functionally inactivates parkin . . . Therefore, the authors proposed that parkin is a direct molecular target of oxidized dopamine, and the dopamine-induced loss of parkin activity represented a possible mechanism of the selective neurodegeneration in PD