Parkinson's Disease Mechanisms and Treatments

Hybrid type-II inhibitors RN277 and RN341 target inactive LRRK2 with far fewer kinase off-targets than Rebastinib, preserve S935 phosphorylation, and rescue kinesin motility in vitro.

This paper introduces UltraID-LIPA, a platform combining optogenetic-induced protein aggregation and proximity biotinylation to identify α-synuclein-interacting proteins, revealing endolysosomal proteins' role in early aggregation.

This study shows that Lrrk2 and Snca gene variants do not affect encephalitis severity in newborn mice infected with reovirus T3D via direct brain inoculation, unlike intranasal infection.

The paper identifies SNX5 knockdown as protective against alpha-synuclein toxicity in a Parkinson's disease cell model through genome-wide RNA interference screening.

The paper identifies presynaptic and postsynaptic risk genes and key connectomes involved in pathological α-synuclein spreading using mathematical models and gene regulatory network analysis.

This study uses fluorescence lifetime imaging to track alpha-synuclein aggregation in neurons, revealing that seeds disassemble before escaping endolysosomes and triggering cytosolic aggregation.

The paper examines T cell responses to PINK1 and α-synuclein in prodromal Parkinson's disease, finding elevated reactivity comparable to clinically diagnosed PD.

This study investigates DNA nanocages loaded with neurotransmitters as a therapeutic approach to clear α-synuclein aggregates in Parkinson's disease models in cells and zebrafish.

This study identifies early immune dysregulation in PINK1 KO mice following intestinal infection, showing myeloid cell activation and T cell response as key factors in PD-like disease progression.

This study investigates how inflammation and IL-4 regulate LRRK2 expression and activity in immune cells, revealing cell-specific effects and the role of the LRRK2-R1441C mutation.

The paper demonstrates that stable CTPR proteins can be modified to bind alpha-synuclein fibrils with micromolar affinity, enabling the testing of fibril-binding peptides.

This study identifies a conserved region in Parkin that mediates its interaction with Miro1, explaining how Parkin targets and ubiquitinates this mitochondrial GTPase.

The paper investigates T cell subsets in Parkinson's disease patients reactive to α-synuclein, finding reduced Granulysin+ CD4 cytotoxic TEM cells and altered CELSR2 expression.

This study predicts Parkinson's dementia using machine learning and multimodal data, finding genetic predisposition and comorbidities as key factors.

This study shows that activating RXR reduces alpha-synuclein pathology and neuroinflammation in a mouse model of Parkinson's disease.

The paper identifies two genes, luna and CG32264, that mediate resistance to paraquat-induced dopaminergic neurodegeneration in Drosophila, with CG32264's mammalian ortholog linked to human Parkinson's disease risk.

This study shows that Pediococcus pentosaceus reduces α-synuclein accumulation and improves motor function in Parkinson's disease models.

The paper stratifies Parkinson's disease stages based on peripheral immune cell responses to stimulation, identifying biomarkers linked to disease progression.

This study identifies how Parkinson's Disease-associated α-Synuclein interacts with histone dimers, revealing structural and functional insights into its role in chromatin regulation.

The paper uses snRNA-seq and spatial transcriptomics to study oligodendroglia in Parkinson's disease, identifying disease-specific subclasses and transcriptomic changes linked to myelin integrity and cell communication.

This study shows that VPS35(D620N) mutation leads to increased glutamate and dopamine transmission in mice, which can be reversed by LRRK2 inhibition.

The paper shows that LRRK2-mutant cases without Lewy bodies have abundant non-inclusion α-synuclein pathology detected by PLA, unlike Lewy body disease cases.

This study examines the distribution of α-synuclein oligomers in LRRK2-related Parkinson's disease, finding a negative correlation between oligomers and Lewy-related pathology.

The paper compares neuroimaging and plasma biomarkers in Lewy body dementia subtypes, finding differences in white matter integrity and plasma markers between dementia with Lewy bodies and Parkinson's disease dementia.

The paper identifies genes regulating alpha-synuclein homeostasis and shows their differential expression correlates with increased rare risk variant burden in Parkinson's disease.

This paper investigates the role of alpha-synuclein in lipid regulation at MAM domains in synucleinopathies, showing disease-specific lipid alterations and Syn's impact on phosphatidylserine metabolism.

The paper examines L-DOPA-induced gene expression changes in the forebrain of mice with progressive dopaminergic neuron loss, identifying region-specific effects and novel genes involved in nonmotor PD symptoms.

The paper investigates mitochondrial complex I deficiency in Parkinson's disease muscle biopsies, finding 9% of cases show reduced CI activity without mtDNA abnormalities.

This study investigates sex-specific effects of environmental toxin-derived alpha synuclein on enteric neuronal-epithelial interactions in a mouse model of Parkinson's Disease, finding increased aSyn and CGRP immunoreactivity in females.

This study shows that SARS-CoV-2 infection synergizes with MPTP to cause neurodegeneration in mice, which is mitigated by vaccination, but not in all genetic backgrounds.