Personal account of the Director of Research at @CureParkinsonsT - All views my own - Kiwi - Kia kaha - 侘寂

London, England
Joined January 2016
New preclinical findings reveal a functional interplay between daily biological timing & lysosomal enzyme regulation, suggesting that optimizing drug dosing & timing of administration may improve the efficacy of GCase-targeted treatments frontiersin.org/journals/cel…
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Proof-of-principle targeting with antisense oligonucleotides demonstrates the feasibility of a cost-effective & scalable approach for allele-specific sequencing of ATXN3 in individual patients & larger Spinocerebellar ataxia type 3 (SCA3) cohorts science.org/doi/10.1126/scit…
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Researchers observe elevated taurochenodeoxycholic acid (TCDCA) in #Parkinsons patients which correlates with disease severity. TCDCA treatment exacerbates rotenone-induced PD mouse model. L. reuteri supplementation⬇️TCDCA & alleviates PD mouse model cell.com/cell-reports-medici…
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Researchers report dopamine⬆️the release of inflammatory cytokine IL-6 in human macrophages in a receptor-dependent manner. Dopamine triggers mitochon. dysfunction & mtDNA release to activate cGAS-STING signaling AND induces a metabolic shift to glycolysis cell.com/cell-reports/fullte…
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"This is particularly relevant to #Parkinsons, where dysregulated dopaminergic signaling, mitochon. dysfunc. & activation of the cGAS-STING pathway are prominent features & is linked with the⬆️release of damaged mtDNA from peripheral blood mononuclear cells from patients with PD"
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New clinical trial registered: An open-label study evaluating brain α-synuclein deposition using XingImaging's PET tracer [¹⁸F]MK-0947 in 18 participants with #Parkinsons clinicaltrials.gov/study/NCT…
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New clinical trial registered: Ginger-PD: Ginger as a Modifier of Ghrelin Levels & Gut Function in #Parkinsons (Ginger-PD); @Marta__Camacho & colleagues are looking for 24 people with PD, 24 REM Sleep Behaviour Disorder, & 24 controls; 12-week study clinicaltrials.gov/study/NCT…
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"A form of #Parkinsons once considered rare is far more common in Pacific communities than previously recognised. Researchers estimate >400 Pasifika people in NZ could be living with a genetic form of the condition linked to a variant in the PINK1 gene" rnz.co.nz/news/science-and-t…
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New research finds the transcription factor B-cell lymphoma/leukemia 11B (BCL11B) is a key regulator of neuroinflammation & dopaminergic survival in models of #Parkinsons; BCL11B promotes neurotoxicity via JAK2/STAT3 activation, inhibition=neuroprotection cell.com/iscience/fulltext/S…
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New research from @neumann_wj et al finds a temporal dissociation within the cortex–basal ganglia network, whereby fast cortical transmission is unaffected by dopamine, which in turn amplifies slower network level communication to the subthalamic nucleus nature.com/articles/s41531-0…
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Researchers find evidence for shared genomic loci (BIN3, MSRA & TNK2 get highlighted) between #Parkinsons & kidney function, offering specific loci & biological pathways for future investigation of the kidney-brain axis in neurodegeneration nature.com/articles/s41467-0…
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New research identifies lysosomal remodeling based on the lysosomal chloride/proton antiporter ClC-7 & Rab accumulation as key features linking PIKfyve inhibition to LRRK2 signaling; Different combinations of Rab & GABARAP inputs activate LRRK2 rupress.org/jcb/article/225/…
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New day, new cholesterol story: Researchers report astrocytic ATP-binding cassette transporter A1 (ABCA1) activity drives excessive cholesterol efflux (in mice), promoting neuronal cholesterol overload. ABCA1 is⬆️in substantia nigra of #Parkinsons brains nature.com/articles/s41593-0…
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"Mechanistically, astrocytic ABCA1 drives excessive cholesterol efflux in mice, promoting neuronal cholesterol overload. In neurons, ABCA1 localizes to lysosomes, where it facilitates cholesterol import, leading to cholesterol accumulation, autophagy impairment & α-syn pathology"
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Genetic silencing of Abca1 in either astrocytes or dopaminergic neurons attenuates neurodegeneration & behavioral deficits in #Parkinsons models. Plus, magnesium citrate is identified as an ABCA1 inhibitor & reduced dopaminergic neuronal loss in a PD mouse model
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