Parkinson's Disease Mechanisms and Treatments

The paper identifies common LRRK2 locus variation associated with survival in progressive supranuclear palsy, linking it to gene expression regulation and suggesting therapeutic implications for tauopathies.

This study shows that IFN-γ and LRRK2 synergize in human neurons and microglia, leading to defects in neurite elongation and microglial activation.

This study investigates sex differences in inflammatory responses and gut microbiota in a progressive monkey model of Parkinson's disease following MPTP treatment.

This study identifies biofluid markers of LRRK2 inhibition in non-human primates using three LRRK2 inhibitors, showing reduced pS935-LRRK2 and exosome LRRK2 in blood, urine, and CSF.

The paper identifies potent small molecules that inhibit toxic alpha-synuclein oligomers and reduce cell death in SH-SY5Y cells using a FRET-based biosensor platform.

The paper identifies gene expression changes in brain regions with gray matter loss in Parkinson's disease and links them to cholinergic circuits and signaling pathways.

The paper reports two new polymorphic structures of alpha-synuclein fibrils solved by cryo-EM, showing distinct structural features and interactions compared to previous structures.

The paper shows that α-synuclein aggregates disrupt pacemaking in vulnerable nigrostriatal dopamine neurons via K-ATP channels, contributing to Parkinson's disease pathogenesis.

This study shows that α-synuclein aggregates cause c-Abl activation via redox stress, leading to neurodegeneration, and that N-acetyl cysteine can block this process in Parkinson's disease models.

The paper combines exome sequencing and array-based comparative genomic hybridization to identify genetic risk factors in familial Parkinson’s disease, finding novel SNVs and CNVs.

This paper demonstrates that antisense oligonucleotides targeting SNCA reduce alpha-synuclein production, prevent pathology, and show translational potential in non-human primates.

This study investigates how cholesterol affects α-Synuclein membrane binding and oligomerization using lipid model systems and biophysical assays.

This study shows that HP-β-CD treatment improves dopaminergic differentiation in PD patient-derived midbrain organoids by enhancing mitophagy.

This study identifies PINK1's role in regulating mitochondrial function, lipid metabolism, and dopamine homeostasis in dopaminergic neurons, showing that cholesterol depletion can reverse PINK1-related phenotypes.

This study shows that mitochondrial dysfunction in Parkinson’s disease models leads to H3K27 hyperacetylation, disrupting active enhancers and epigenetic regulation.

This study shows that the STING pathway does not contribute to Pink1/parkin phenotypes in Drosophila, contrasting findings in mice.

This study shows ATF4 promotes neuronal death in Parkinson’s Disease models by inducing pro-apoptotic genes and that inhibiting ATF4 protects against neurotoxin-induced cell loss.

The paper uses 3D multicolor STED microscopy to study subcellular distribution of alpha-synuclein variants in Parkinson’s disease brains, revealing their association with pathology.

This study finds increased hypothalamic diffusivity in Parkinson's disease patients with high autonomic symptom burden compared to those with low burden.

The paper uses a genetic model to study transcriptome changes in dopamine-depleted mice, finding DA-dependent gene expression in SNc that suggests a protective role for dopamine.

This study shows that overexpressing α-synuclein in the retina causes dopamine amacrine cell loss and visual impairment, which can be rescued by L-DOPA.

This study identifies shared genetic loci between multiple system atrophy and inflammatory bowel disease using conjFDR, highlighting immune and gut-related molecular mechanisms.

This study identifies RasGRP1 as a key mediator of L-DOPA-induced dyskinesia in a mouse model of Parkinson's disease, showing its role in multiple signaling pathways and potential as a therapeutic target.

This study investigates the role of parkin in maintaining gut microbiota in Drosophila parkinsonism models, finding that parkin loss increases bacterial load and that germ-free conditions improve paraquat resistance.

The paper models the role of α-synuclein and dopamine in cell death in Parkinson’s disease, showing how mutations affect toxicity through oxidative stress and dopamine pathways.

This study downregulates PMCA in dopaminergic neurons of Drosophila to model Parkinson's Disease, finding increased calcium, oxidative stress, locomotor changes, and lifespan reduction.

The paper examines the correlation between CSF sTREM2 and CSF tau levels in Parkinson’s disease and finds that sTREM2 is elevated in PD subgroups with abnormal tau but not Aβ.

This study shows that reduced beta desynchronization in Parkinson’s disease is linked to impaired memory formation.

This study identifies distinct subtypes of freezing of gait in Parkinson's disease based on levodopa responsiveness, showing ONOFF-FOG differs from OFF-FOG in clinical outcomes and response to treatment.

The paper identifies 12 dysregulated genes shared between brain and blood cells in Parkinson's disease using transcriptomic and eQTL data, validated with dbGaP.