New research results indicate that serum changes in dopa decarboxylase, prolactin, & AOC3 primarily reflect treatment exposure rather than disease biology, highlighting the need to account for medication effects in proteomic studies (Go Ludo!) www.nature.com/articles/s41...

Single nuclear RNA seq shows altered microglial & astrocytic functions in post-mortem #Parkinsons; Upregulation of chaperone protein folding functions Hey editors at BMC Genomic Data: This manuscript has no figures attached link.springer.com/article/10.1...

Researchers report inhibiting 15-PGDH restores redox homeostasis & confers neuroprotection in MODELS OF #Parkinsons www.sciencedirect.com/science/arti...

Interesting preprint manuscript: Researchers used network analysis to identify a specific sham surgery-related pattern in metabolic PET data from a double-blind #Parkinsons gene therapy trial; An imaging marker of placebo susceptibility in PD trials www.researchsquare.com/article/rs-1...

The road towards faster development of novel pharmacotherapies for persons with #Parkinsons - a special issue of the Journal of PD journals.sagepub.com/doi/10.1177/...

By analyzing #Parkinsons patients & LRRK2 gain-of-function mice, researchers proposed that PD represents an accelerated aging disorder driven by STING-dependent inflammation www.cell.com/cell-reports...

New research reveals 2 anatomically & functionally distinct populations of subthalamic nucleus neurons involved in levodopa-induced dyskinesia regulation, offering insights into the circuitry underlying subthalamic nucleus-deep-brain stimulation www.science.org/doi/10.1126/...

A #Parkinsons drug screen on induced pluripotent stem cells from a PARK9 patient carrying an ATP13A2 mutation identified 19 candidate compounds that reduced autophagosome accumulation (including paroxetine, Ro 25-6981, amisulpride, & PK11195) onlinelibrary.wiley.com/doi/10.1111/...

Multimodal neuroimaging (combining ¹⁸F-FPCIT dopamine transporter PET/MRI, quantitative susceptibility mapping, & diffusion MRI tractography) elucidates the posterior-to-anterior gradient of nigrostriatal degeneration in #Parkinsons (n=48 PD+10 controls) www.nature.com/articles/s41...

New study suggests #Alzheimers -related CSF signature may define a subgroup of progressive supranuclear palsy #PSP with shortened survival. The p-tau/Aβ42 ratio could offer a pragmatic prognostic tool for patient stratification movementdisorders.onlinelibrary.wiley.com/doi/10.1002/...

New research identifies lipid droplets as drivers of aberrant α-synuclein phase separation & suggest that lipid droplet-rich condensates contribute to mitochondrial dysfunction & impaired energy homeostasis link.springer.com/article/10.1...

Researchers have identified the bridge-like lipid transport protein VPS13C/PARK23 as a key component of a global early response pathway to lysosome damage; New insights into how loss-of-function mutations in VPS13C may enhance the risk of #Parkinsons www.nature.com/articles/s41...

The α-Synuclein aggregation landscape - new review provides a nutshell overview, from phase separation to neurotoxic intermediates febs.onlinelibrary.wiley.com/doi/10.1002/...

A new #publication from CRN Team Alessi maps lysosomal protein composition across major brain cell types, revealing cell-type diversity and identifying SLC45A1 as a neuron-specific lysosomal protein tied to lysosomal dysfunction. 🔗 bit.ly/3QsxZEM

Interesting: Researchers previously screened an FDA approved compound library for TMEM175 modulators. Now, they present data on the most potent hit, candesartan cilexetil, with the cilexetil handle being the key pharmacophoric element journals.physiology.org/doi/abs/10.1...

"Convergent quantitative evidence points to a substantial vesicular storage defect in residual dopaminergic terminals in #Parkinsons". Findings challenges the sufficiency of nigrostriatal dopaminergic denervation alone to account for motor phenotype of PD www.neurology.org/doi/10.1212/...

Using longitudinal imaging data to model the progression of cardiac sympathetic & nigrostriatal dopaminergic degeneration, researchers use the resulting curves to estimate the prodromal period of Body-first Lewy body disease www.nature.com/articles/s41...

New data suggests that "air pollution may contribute to #Parkinsons through inflammation, oxidative stress, & mitochondrial dysfunction"; Serum samples collected from 616 PD patients & 271 controls in central California www.nature.com/articles/s41...

Could cerebrospinal fluid turnover dysfunction be a hidden early biomarker in REM sleep behavior disorder? New research indicates⬆️CSF & perivascular spaces volumes in iRBD without a matching increase in drainage venous structures; Impaired CSF filtration? www.nature.com/articles/s41...

"Distinct neuropsychological profiles & trajectories emerge in #Alzheimers & dementia with Lewy bodies depending on underlying pathology" - a retrospective longitudinal study of 350 individuals highlights trajectory differences www.neurology.org/doi/10.1212/...

Researchers report blood-based circular RNAs as possible biomarkers for early diagnosis of #Alzheimers; 34 circRNAs were comparable to plasma phosphorylated Tau-217 www.nature.com/articles/s41...

Researchers found variations of global brain asymmetry & they identified disease-specific alterations in brain asymmetry across aging-related conditions, including #Parkinsons; Also a “left hemi-aging” pattern that challenges the “right hemi-aging” model www.science.org/doi/10.1126/...

A new genome-wide screening study in macrophages finds that the signaling molecule PLCG2 acts as a negative regulator of #Parkinsons -related GCase; Depleting PLCG2 =⬆️ trafficking of GCase to the lysosome & restored lipid clearance in GCase mutant cells www.pnas.org/doi/10.1073/...

Useful new tool for #Parkinsons research: A stem cell toolkit that facilitates cellular & molecular analysis of 23 distinct lysosomal storage disorder genes, including the majority of genes responsible for sphingolipidoses or neuronal ceroid lipofuscinoses www.pnas.org/doi/10.1073/...

A post hoc analysis of samples from the low-dose lithium trial finds lithium therapy was associated with a significant reduction in serum neurofilament light chain in #Parkinsons www.ibroneuroreports.org/article/S266...

Oligodendrocytes The LRRK2 gene is expressed at significantly higher levels in oligodendrocyte precursor cells compared to other cell types in the substantia nigra Single-cell RNA seq of oligodendroglial lineage cells derived from iPSCs provides insights www.cell.com/iscience/ful...

New review explores a "new dawn with pluripotent stem cell–based therapy" for cell transplantation therapy in #Parkinsons onlinelibrary.wiley.com/doi/10.1111/...

Researchers provide new insights into how #Parkinsons -associated LRRK2-G2019S mutation disrupts the astrocytic physiological localization of D2R, may impair protective dopamine signaling, resulting in increased neuroinflammation & neuronal damage onlinelibrary.wiley.com/doi/10.1111/...

Researchers report that #Parkinsons patients undergoing deep brain stimulation for medically refractory motor fluctuations or dyskinesias do not present with PFC Lewy body pathology at the time of neurosurgery; 97.6% (n = 204/209); DBS selection process? www.nature.com/articles/s41...

VERY interesting: Bridge Analytics emerges from stealth providing a platform for researchers to use "traditional analytics & advanced data science methods to help researchers query complex datasets in a shared quest to find cures" for #Parkinsons, ASD & BP bridgeanalytics.webflow.io

Researchers fail to replicate previous work suggesting that repeated gastrointestinal infection with Citrobacter rodentium can induce #Parkinsons-like motor dysfunction in Pink1 knockout mice journals.plos.org/plospathogen...

"Health inequalities have worsened, with middle & high-middle SDI regions, especially East Asia & Andean Latin America, exhibiting the fastest growth rates" - Global regional & national burden & trends of early-onset #Parkinsons from 1990 to 2021 www.nature.com/articles/s41...

Dysregulation of the TFEB-ATP6V0C axis in microglia exacerbates α-synuclein pathology through impaired lysosomal acidification in models of #Parkinsons; Both TFEB activation & mTOR inhibition restore lysosomal acidity & upregulate ATP6V0C expression www.nature.com/articles/s41...

The German DZNE is coordinating a German-US consortium that has been awarded a $3.5M grant to develop reliable, openly accessible antibodies that enable researchers to investigate disease-related changes in #Parkinsons in the brain & other tissues www.dzne.de/en/im-fokus/...

Aspen Neuroscience announces completion of dosing in Cohort 3 & Cohort 4 of their ongoing Phase 1/2a ASPIRO clinical trial evaluating sasineprocel (ANPD001 -a cell transplantation product) for the treatment of #Parkinsons aspenneuroscience.com/aspen-neuros...

Gain Therapeutics announces that the US FDA has authorized their Investigational New Drug (IND) application for GT-02287 (a GCase activator) allowing them to initiate Phase 2 clinical testing in #Parkinsons patients with or without a GBA1 mutation in the U.S gaintherapeutics.com/newsroom/pre...

New review covers the current understanding of mitochondrial quality control biology in the context of healthy human longevity, exploring the regulation of MQC in physiological conditions & the dysregulation of MQC in ageing www.nature.com/articles/s42...

New review explores immune signaling pathways in astrocytes, including pattern recognition through Toll-like receptors, nucleic acid sensors & inflammasomes; Highlighting unresolved questions regarding the immune functions of astrocytes www.nature.com/articles/s41...

New evidence that bee venom (yes, bee venom) "may serve as a promising adjuvant to L-DOPA/carbidopa, improving both motor & cognitive outcomes in a mouse model of #Parkinsons" (6-OHDA); Anyone keen for a clinical trial? onlinelibrary.wiley.com/doi/10.1002/...

New review summarises the current understanding of how adaptive immunity can shape the progression of neurodegenerative conditions & highlights cross-disease parallels & potentially shared mechanisms www.nature.com/articles/s41...

Useful viewpoint addressing the challenges of translating LRRK2 biology into disease-modifying therapies for #Parkinsons, & highlighting the LRRK2 Investigative Therapeutics Exchange (LITE) initiative movementdisorders.onlinelibrary.wiley.com/doi/10.1002/...

Researchers present new immunoassays that complement previously established PINK1 & p-S65-Ub measurements, "enhancing mechanistic insight into mitophagy & enabling effective monitoring of #Parkinsons therapies & other neurodegenerative diseases" www.tandfonline.com/doi/full/10....

New research finds that #Parkinsons -relevant modifications can modulate α-Syn phase behavior, both in pathological & physiological contexts; familial variants tested included A30P, H50Q, G51D & A53T www.nature.com/articles/s41...

New research using data of the German National Cohort (NAKO; N=205K participants) presents a comprehensive assessment of lifecourse & mortality of #Parkinsons; PD prevalence was 0.13%, but it was 2.5-fold higher in claims data www.nature.com/articles/s41...

"In this small study of autopsy-confirmed incidental Lewy body disease, aSyn seeding assays had moderately high sensitivity (75.8%) in the CSF but not in skin or submandibular gland"; #Parkinsons=high sensitivity, specificity similar in all tissues www.neurology.org/doi/10.1212/...

Interesting: colony stimulating factor 1 receptor (Csf1r) inhibition in a preclinical model of inflammatory bowel disease (IBD) did not locally ameliorate colitis, but it did provide neuroprotection to dopaminergic neurons link.springer.com/article/10.1...

"Overexpression of phosphorylated & truncated α-Syn monomers was insufficient to drive fibrillar aggregation, neurodeg., or (non-) motor symptoms relevant to #Parkinsons", suggesting that additional drivers are required to recapitulate the pathogenesis www.nature.com/articles/s41...

Useful review on the rationale & current status of fecal microbiota transplantations for #Parkinsons; "All current trials show that FMT is a safe procedure"; "Clinical response is variable (including positive effects in placebo groups)" journals.sagepub.com/doi/10.1177/...

Researchers used the Roche #Parkinsons Mobile Application version 2 (a smartphone-based platform) to monitor progression in idiopathic REM sleep behavior disorder; Findings support digital bradykinesia as a sensitive endpoint for prodromal PD trials www.nature.com/articles/s41...

The protocol for the Steps against the burden of #Parkinsons disease (StepuP) study has been published. This is a randomized controlled trial elucidating the biomechanical & neurophysiol. mechanisms of a speed dependent treadmill training intervention journals.plos.org/plosone/arti...