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

"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"

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…

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/…

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…

Curiously, both of these ARBs are traditionally considered non-CNS penetrant "both produce insurmountable, slowly reversible AT1 blockade with prolonged receptor residence times, whereas losartan binds in a surmountable, rapidly dissociating manner"

Using large-scale hospital electronic health records of the University of California health system (n=890K hypertensive patients), researchers report Angiotensin receptor blockers irbesartan & olmesartan were associated with lower incident #Parkinsons risk onlinelibrary.wiley.com/doi/…

XellSmart presented 6 months post-transplant data for their Phase I trial of their off-the-shelf #Parkinsons cell therapy XS411, & announces successfully completion of enrollment for the Phase 2 trial of XS411 prnewswire.com/news-releases…

Something researchers to explore: The GBA1 Canada initiative (G-can) - a pre-competitive, collaborative, open-science platform accelerating research & treatment development for GBA1-related #Parkinsons journals.sagepub.com/doi/10.…

New research suggests dietary patterns/habits in isolated REM sleep behavior disorder is associated with gut microbiome dysbiosis & predicts neurodegenerative progression, highlighting diet–microbiome interactions as modifiable factors movementdisorders.onlinelibr…

Researchers virtually screen of 9.4k compounds (2.6k FDA-approved drugs, 6.7k African natural products) against the ATP-binding pocket of LRRK2-G2019S, & identify Rimonabant, Gallagic acid, Acalabrutinib, & Atovaquone as repurposable candidates nature.com/articles/s41598-0…

Researchers report a case of #Parkinsons caused by a de novo SNCA triplication with longitudinally evaluated gene expression in whole blood & platelets at 2 disease stages: early PD (age 41) & Parkinson's disease dementia (age 44) movementdisorders.onlinelibr…

New research from the GP2 team finds that the GCH1 p.Ser80Asn variant is a rare, East Asian-enriched risk variant for #Parkinsons movementdisorders.onlinelibr…

Another week, another paper for @GeorgeTofaris & colleagues This week, they report the epitope accessibility & topology of extracellular vesicle-associated α-synuclein proteoforms, rather than their abundance alone, discriminate synucleinopathy subtypes academic.oup.com/brain/advan…

New review explores resilience & vulnerability in the midbrain dopamine system during aging; "Elucidating these neuroadaptive mechanisms could offer a path toward preserving dopamine neuron function across the lifespan" & possibly preventing neurodegen. cell.com/trends/neuroscience…