Personal account of the Director of Research at @CureParkinsonsT - All views my own - Kiwi - Kia kaha - 侘寂
London, England
Joined January 2016
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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…
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…
"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"
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…
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…
"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…
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…
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…
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…
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/…
Nice editorial from @pfeffersuzanne regarding this research:
rupress.org/jcb/article/225/…
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…
"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"
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
Wonderful short film from Zaina Khan exploring young onset #Parkinsons (@CamilleBCarroll, @Ladybale & yours truly make cameos)
youtube.com/watch?v=NB17gyfB…
Researchers report a pathological role for α-synuclein in the CNS border tissues & position meningeal immunity as a contributor to CNS clearance deficits in #Parkinsons; α-syn at CNS borders⬆️CSF TNF & both impair lymphatic endothelial cell function
rupress.org/jem/article/223/…
Researchers report that #Parkinsons-associated LRRK2 mutations "converge on disrupted iron homeostasis across multiple human neural cell types", supporting a link between LRRK2 signaling, lysosomal iron dysregulation & ferroptosis-related stress
link.springer.com/article/10…
Viral Desulfovibrio (DSV) species have been linked to #Parkinsons. Now researchers report that DSV-derived viability-dependent processes (including metabolic activity) more strongly promote alpha-synuclein aggregation & toxicity than structural component
sciencedirect.com/science/ar…
Movement disorders neurology remains an act of watching. @janealty1 & @vertigologist explore computer vision for the detection of deterioration in #Parkinsons. But if "no effective intervention or care response is available, have we actually helped"?
nature.com/articles/s41531-0…
Mission Therapeutics @MISSIONTherapeu announces dosing of first #Parkinsons patient in the Phase 1b study of their USP30 inhibitor MTX325. The study is taking place in UK, Europe & Australia. Readout is anticipated in late 2027
missiontherapeutics.com/miss…
