Parkinson's Disease Mechanisms and Treatments

This study shows that α-synuclein accumulation in dopaminergic neurons leads to mitochondrial dysfunction and changes in circadian gene expression, contributing to neuronal damage in Parkinson's disease.

This study shows that disrupting Lrrk2 function in both directions leads to T cell dysregulation and exhaustion-like immune responses in mice.

The paper profiles PBMCs from PD patients and controls using single-cell RNA sequencing after ex vivo activation, finding sex-convergent CD8+ T cell exhaustion associated with disease.

The paper analyzes longitudinal histopathology data to show that α-synuclein pathology follows rise-and-fall dynamics, revealing a vulnerability axis linked to energy metabolism and monoaminergic neurons.

The paper shows that REM sleep suppresses β oscillations in Parkinsonism, allowing rapid movements despite motor impairments during wakefulness.

This study examines mitochondrial calcium homeostasis and bioenergetics in hiPSC-derived astrocytes with LRRK2 and PRKN mutations, finding altered calcium dynamics and mitochondrial morphology in PD-related mutants.

The paper shows that CASIN inhibits CDC42, reversing PD-related transcriptional changes and affecting MAPK and PI3K/AKT pathways in an aging mouse model.

This study shows that inhibiting mitochondrial complex III with pesticides causes dopaminergic neurotoxicity in C. elegans through redox stress, which can be mitigated by antioxidants.

This study shows that Pink1 loss in Drosophila disrupts ensheathing glia, leading to dopaminergic synapse loss, and identifies vesicle trafficking factors as potential therapeutic targets.

This study investigates the effort-reward trade-off in Parkinson's disease, finding increased effort perception but no reduced reward sensitivity or biased effort-reward mapping.

This study shows that LRRK2 G2019S mutation in mice, when combined with recurrent bacterial infection, leads to Parkinson's-like pathology.

The paper shows that G51D alpha-synuclein mice exhibit loss of primary cilia and neurotrophic signaling in specific brain regions, linking ciliary dysfunction to Parkinson's disease pathology.

This paper elucidates the structural mechanisms by which LRRK2 is activated and autoinhibited, showing how mutations affect these processes and suggesting therapeutic strategies.

This study identifies NDK as a key gene at the intersection of guanosine nucleotide metabolism and bioenergetics, showing its protective role in Parkinson's disease and its association with genetic risk.

This study shows CBD protects neurons from 6-OHDA toxicity by preserving Nrf2 function and mitochondrial integrity through antioxidant mechanisms.

This study shows the G2019S LRRK2 mutation alters transcriptomes of myeloid cells under proinflammatory conditions, affecting lipid metabolism and phagocytic function.

This study compares soluble α-synuclein species from MSA and LBD brains, finding differences in their seeding activity and size distribution.

This study shows that α-synuclein aggregates in corticostriatal terminals impair glutamatergic transmission without causing neurodegeneration.

This study identifies age-dependent neuroinflammatory changes in NM-containing neurons linked to neurodegeneration, with GPNMB as a conserved protective factor in Parkinson's disease.

This study shows that LRRK2 regulates synaptic function by modulating actin cytoskeletal dynamics through BDNF signaling in neurons.

The paper investigates the genetic role of SLC25A46 in Parkinson's disease, REM sleep behavior disorder, and Dementia with Lewy Bodies, finding no significant associations.

The paper characterizes the genetic landscape of Parkinson's disease in a Chilean cohort, identifying common pathogenic variants in LRRK2 and GBA1.

This study shows that astrocytes in the substantia nigra pars compacta of A53T transgenic mice have more -synuclein aggregates and reactive morphology compared to wild-type mice.

This study identifies age- and dopamine-dependent synaptic and cellular changes in M1 neurons during progressive parkinsonism and shows that L-DOPA can prevent or rescue these adaptations.

This study develops an optimized Nano-QuIC platform to detect alpha-synuclein oligomers in human plasma with high sensitivity for early Parkinson's disease diagnosis.

The paper develops a peptide, PEP 3, that disrupts the LRRK2/PP1 interaction and shows promise as a therapeutic for Parkinson's disease by reducing dopaminergic cell death and alpha-synuclein phosphorylation.

This study identifies LRRK2's role in impairing dopamine axon release sites in Parkinson's disease, leading to reduced dopamine release and synaptic dysfunction.

Proximity proteomics in PFF-seeded mouse olfactory bulb shows aggregated phospho-S129 alpha-synuclein mostly reprioritizes existing interactions toward axon-glia, myelin and proteostasis proteins, with a conserved 107-protein signature.

This study shows that LRRK2 mutations disrupt iron homeostasis in neurons and astrocytes, leading to oxidative stress and ferroptosis.

This study shows genipin rescues sleep deficits caused by α-synuclein toxicity in Drosophila melanogaster.