Parkinson's Disease Mechanisms and Treatments

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.

Profiling peripheral immune cells in Parkinsons disease: A Scoping Review

This review synthesizes findings on peripheral immune cell changes in Parkinson's disease, identifying common immune signatures and methodological inconsistencies across studies.

A 'brain-first' mouse model of progressive alpha-synuclein pathology via intranasal rotenone administration

This study develops a mouse model of Parkinson's disease by intranasal rotenone administration, showing progressive alpha-synuclein pathology from the olfactory bulb to other brain regions.

Altered Striatal Acetylcholine Dynamics in a Model of Parkinson Disease and L-DOPA-induced Dyskinesia

This study investigates how dopamine depletion and L-DOPA treatment alter acetylcholine dynamics in the striatum of a Parkinson's disease model, revealing state-dependent changes in temporal organization of cholinergic signaling.

Cross-species molecular stratification enables T cell receptor diagnosis of Parkinson's disease

This paper stratifies Parkinson's disease patients using T-cell receptor repertoires and develops classifiers that achieve high AUC for subtype diagnosis.

Cross Dataset Transcriptomic Analysis Identifies Oxidative Stress Inflammation Gene Networks Modulated by Nutrigenomic Interventions in Parkinson Disease

The paper identifies oxidative stress and inflammation gene networks in Parkinson's disease through cross-dataset transcriptomic analysis and nutrigenomic integration, revealing candidate diet-gene associations.

Probing the energy landscape of α-Synuclein amyloid fibril formation by systematic K-to-Q mutagenesis

This study uses systematic K-to-Q mutagenesis to probe the energy landscape of α-Synuclein aggregation, identifying core residue mutations that alter free energy pathways and fibril polymorphism.

An atfs-1 loss-of-function screen identifies novel regulators of a-synuclein toxicity in C. elegans dopaminergic neurons

Dual effect of alpha-synuclein disease variants on condensate formation

This study shows that specific Parkinson's disease-associated alpha-synuclein variants either enhance or impair condensate formation, highlighting divergent pathways in disease pathology.

Progression GWAS followed by functional characterization implicates E3 ubiquitin ligase TRIM2 as a potential genetic modifier of Parkinson's Disease progression

The paper performs a GWAS on PD progression metrics and identifies TRIM2 as a genetic modifier, showing its role in regulating neurofilament light and alpha-synuclein aggregation.

Activation of transposable elements is linked to a region- and cell-type-specific interferon response in Parkinson's disease

The paper investigates TE transcription in Parkinson's disease brains, finding region- and cell-type-specific TE activation linked to an interferon response in microglia and neurons.

Parkinson's disease-linked D620N mutation selectively alters the brain-specific protein interactome of VPS35

This study identifies a selective effect of the D620N VPS35 mutation on the brain-specific protein interactome in mammalian cells and brain tissue.

Olfactory proteomics reveals the capacity of the HDAC1 inhibitor pyroxamide to halt the α-synuclein preformed fibrils-induced damage in nasal epithelial, microglial and dopaminergic neuronal cell lines

The paper uses proteomic analysis of the olfactory tract to identify pyroxamide, an HDAC1 inhibitor, as a potential therapeutic for Parkinson's disease by reducing α-synuclein fibril-induced toxicity in cell lines.

Intranigral injection of Alpha-Synuclein pre-formed fibrils leads to BBB compromise and Bilateral Dopaminergic Neurodegeneration in A53T Alpha-Synuclein transgenic mice.

This study develops a mouse model of Parkinson's disease by injecting alpha-synuclein pre-formed fibrils, leading to bilateral dopaminergic neurodegeneration and BBB compromise.

Leveraging the salivary microbiome profile to stratify REM sleep behavior disorder and synucleinopathies

The paper uses salivary microbiome profiles to stratify REM sleep behavior disorder and synucleinopathies, finding distinct microbial signatures that distinguish these conditions.

Protein aggregation inhibitors induce divergent transcriptional responses in a cellular model of a-synuclein seeded aggregation

The paper evaluates three Syn aggregation inhibitors in a cellular model of a-synuclein aggregation using single-cell RNA sequencing to identify transcriptional changes and potential druggable pathways.

Inhibition of mitochondrial complex III causes selective dopaminergic neurotoxicity by redox stress in Caenorhabditis elegans

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.

PARKINSON'S DISEASE-ASSOCIATED PINK1 LOSS DISRUPTS ENSHEATHING GLIA AND CAUSES DOPAMINERGIC NEURON SYNAPSE LOSS

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.

Impaired effort perception, not reward sensitivity, impacts the effort-reward trade-off in Parkinsons disease

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.

Selective loss of Primary Cilia and Neurotrophic Signaling in G51D alpha-Synuclein Mice Highlights a Common Pathway to Parkinsons Disease

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.

The structural basis for LRRK2's activation and autoinhibition

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

Cannabidiol confers neuroprotection against 6-OHDA toxicity by rescuing Nrf2 proteostasis and preserving mitochondrial integrity

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

LRRK2 G2019S variant is associated with transcriptional changes in Parkinson's disease human myeloid cells under proinflammatory environment

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

LRRK2 regulates synaptic function through modulation of actin cytoskeletal dynamics

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

Lack of genetic evidence for a role of SLC25A46 in alpha-synucleinopathies

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.

Transgenic A53T mice have astrocytic α-synuclein aggregates in dopamine and striatal regions

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.

Ultrasensitive Detection of Alpha-Synuclein Oligomers in Human Plasma Using Optimized Nano-QuIC

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.

Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons

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

Parkinson's disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes

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

Complement Dysregulation During the Early Phases of Synucleinopathy

This study shows that synucleinopathy triggers complement activation and dysregulation before neurodegeneration in a rat model and human Parkinson's disease tissue.