Parkinson's Disease Mechanisms and Treatments

Levodopa induced dyskinesia severity is linked to distinct microstructural alterations in nigrostriatal and brainwide neural circuits

This study investigates how L-DOPA-induced dyskinesia (LID) relates to microstructural changes in brain circuits, finding brainwide alterations beyond the nigrostriatal system.

The Parkinson's disease-associated A53E mutation decreases alpha-synuclein aggregation and phosphorylation in vivo

This study shows that the A53E mutation in alpha-synuclein reduces aggregation and phosphorylation in vivo, leading to delayed progression of Parkinson's disease.

Oxidized EGCG redirects α-synuclein aggregation through shear-selected interactions

This study shows that oxidized EGCG, not unoxidized EGCG, binds α-synuclein, inhibits fibrillation, and remodels fibrils, with shear flow affecting these interactions.

Neuroinflammation is an early pathological process in a mouse model of prodromal Parkinsons disease

This study shows that neuroinflammation occurs early in a mouse model of prodromal Parkinson's disease before neuronal loss, linking Syn pathology to olfactory dysfunction.

L-DOPA Rescues Reach Height but Not Trajectory Area in a Bimanual String-Pulling Behavior in Parkinsonian Rats

This study shows that L-DOPA improves certain motor features but not others in a bimanual string-pulling task in Parkinsonian rats.

Neuroprotective activity of sub-anesthetic ketamine in a preclinical model of Parkinson's disease is not blocked by antagonizing brain-derived neurotrophic factor signaling

This study shows that low-dose ketamine protects against Parkinson's-like motor deficits in rats without relying on BDNF-TrkB signaling.

Parkinson's disease genetic risk converges on Lewy body pathology-associated microglial states

The paper identifies microglial states associated with Parkinson's disease genetic risk and Lewy body pathology using single-cell profiling and integrates data with AMP PD.

Parkin deficiency rewires the genetic dependencies that govern neuronal survival

This study shows that Parkin deficiency alters genetic dependencies for neuronal survival, identifying key pathways and genes involved in this rewiring.

Novel LRRK2 Kinase Inhibitors Enhance Phosphorylation and Restore Adapter Protein Binding in LRRK2 Variants

This study evaluates two series of LRRK2 inhibitors, showing that series B compounds enhance phosphorylation and restore 14-3-3 binding in LRRK2 variants, suggesting conformation-selective inhibition as a potential PD therapy.

Cortical pyramidal tract neurons constrain pathological dopaminergic motor responses

This study shows that activating pyramidal tract neurons in the motor cortex reduces pathological dopaminergic motor responses in mice with Parkinson's-like symptoms.

Genetic Modifiers of Age at Onset for Parkinson's Disease in European Populations

This study identifies five genetic loci associated with age at onset of Parkinson's disease in European populations, including novel associations at HIP1R and FSCB.

Hsp10 Targets the C-Terminus of α-Synuclein to Inhibit Secondary Nucleation and Remodel Labile Fibrils

This study identifies how Hsp10 interacts with α-synuclein to inhibit its aggregation and remodel fibrils, revealing a mechanism for its role in Parkinson's disease.

Alpha-synuclein and neuromelanin converge to promote Parkinsons disease pathology

This study identifies a bidirectional pathogenic relationship between alpha-synuclein and neuromelanin in Parkinson's disease, showing they promote each other's accumulation and neuronal loss.

Dysregulation of miR-103a-3p/AGFG1 axis links endocytic trafficking dysfunction to ER stress in Parkinson's disease

This study identifies the miR-103a-3p/AGFG1 axis as a molecular link between endocytic trafficking dysfunction and ER stress in Parkinson's disease, with AGFG1 as a potential therapeutic target.

Modelling prodromal Parkinson's disease- gastrointestinal pathology and early motor deficits in mice after transient rotenone exposure

This study models prodromal Parkinson's disease in mice by exposing them to rotenone, revealing GI dysfunction and early brain pathology without significant motor deficits.

Examining the Atypical Structure Adopted by the 37-51 Segment of α-synuclein in the Early Stage of Aggregation

This study uses molecular dynamics simulations to identify a previously unreported braid conformation in the 37-51 segment of α-synuclein that may influence aggregation.

Splanchnic-spinal transmission of gut-initiated α-synucleinopathy

This study shows that gut-initiated α-synucleinopathy spreads via the splanchnic-spinal pathway, not just the vagus nerve, and identifies spinal pathology in human Parkinson's disease.

Lewy pathology accumulates in swollen corticostriatal synapses in α-synucleinopathies

The paper quantifies Lewy pathology burden in the putamen across Lewy body diseases and finds it accumulates in excitatory synapses before synaptic degeneration.

PODXL regulates the neuronal entry of α-synuclein aggregates

This study identifies PODXL as a suppressor of α-synuclein fibril uptake in neurons, highlighting its glycan-dependent surface properties and interaction with MME.

Effects of Cyperus Esculentus Infused Diet on the Hippocampus in Rotenone-Induced Parkinson-like Disease Model in adult male Wistar Rats; a preliminary study.

This study evaluates the neuroprotective effects of tiger nut-infused diet on rotenone-induced hippocampal damage in rats, finding partial protection against oxidative stress and histopathological changes.

Enhancement of gut-microbiome-based classification of prodromal Parkinson's Disease cases by hyperparameter tuning, integration of multimodal data, and meta-analysis.

This study improves classification of prodromal Parkinson's Disease using gut microbiota data and clinical features, achieving an AUC of 0.917 with integrated multimodal data.

Brainstem cholinergic cell loss causes slowly-developing motor impairments

This study develops a mouse model of brainstem cholinergic cell loss to show delayed motor impairments and circuit reorganization in Parkinson's disease.

Sex- and age-dependent control of dopamine function by LRRK2, and rapid reversal of dopamine release deficits in the LRRK2-G2019S knock-in mouse model of Parkinson's Disease.

The paper investigates how LRRK2 activity affects dopamine release in mice, showing age- and sex-dependent changes and rapid reversal with inhibition in certain groups.

When longevity becomes chemistry: Why rodent brains lack neuromelanin

The paper shows that mole rats accumulate neuromelanin with age, suggesting that long-lived rodents develop this pigment, while short-lived rodents like mice and rats do not reach detectable levels due to their shorter lifespans.

Cross Study Regulator Activity Analysis Reveals Convergent Programs in alpha Synuclein PFF Models of Parkinson Disease

The paper analyzes regulator activity across mouse PFF Parkinson disease models and human PD data, identifying shared transcriptional programs in dopaminergic identity, protein homeostasis, and inflammation.

Reverse engineering Lewy bodies suggests alpha-synuclein pathology as condensatopathy

The paper shows that alpha-synuclein phase separation can form Lewy body-like structures without pre-existing seeds, suggesting a new mechanism for neurodegeneration.

Title: Unilateral loss of tyrosine hydroxylase in adult midbrain dopaminergic neurons reveals reduction to neuregulin1 in rat model of acute dopaminergic dysfunction

This study creates a rat model of adult dopamine loss by knocking out tyrosine hydroxylase and identifies early transcriptional changes, including reduced neuregulin1, in dopaminergic neurons and surrounding cells.

Intrastriatal injection of amplified Lewy body dementia (LBD) fibrils in mice results in accumulation of fibrils with LBD structure and neurodegeneration

The paper shows that injecting amplified Lewy body dementia fibrils into mice leads to fibril accumulation with LBD structure and neurodegeneration.

Astrocyte-Specific dsRNA-ADAR1 Signalling Links Innate Immunity to Complement Activation in Parkinson Disease

The paper identifies astrocytes as a key site of dsRNA accumulation and ADAR1 p150 induction in Parkinson's disease, linking dsRNA sensing to complement activation in a cell-type-specific manner.

A Bayesian approach to volumetric analysis in rare neurodegenerative disorders

This paper applies Bayesian hierarchical modeling to assess regional brain atrophy in rare neurodegenerative disorders, finding significant volume loss in specific brain regions across disease groups.