Parkinson's Disease Mechanisms and Treatments

Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases

This study reports the atomic structure of mouse α-synuclein fibrils and shows they differ structurally and functionally from human fibrils linked to Parkinson's and MSA.

Amyloid Accelerator Polyphosphate Implicated as the Mystery Density in α-Synuclein Fibrils

This study identifies polyphosphate as the 'mystery density' in α-synuclein fibrils by showing it binds to lysine residues, affecting fibril formation and toxicity.

DJ-1 mediates regulation of metabolism and immune response in Parkinsons disease astrocytes and Glioblastoma cells

This study shows DJ-1 affects metabolism and immune response differently in Parkinson's disease and glioblastoma cells, with antioxidant treatment rescuing PD-related phenotypes.

α-Synuclein Overexpression and the Microbiome Shape the Gut and Brain Metabolome in Mice

This study shows that α-synuclein overexpression and the microbiome alter the gut and brain metabolome in mice, with TMAO levels correlating across tissues and linking to PD-like outcomes.

Single-cell transcriptomic and proteomic analysis of Parkinson's disease Brains

The paper performs single-cell transcriptomic and proteomic analysis of Parkinson's disease brains, identifying cell-type-specific changes and differences from Alzheimer's disease.

Impaired maturation of wild-type superoxide dismutase 1 associated with neurodegeneration in Parkinson disease brain and a novel murine model

The paper investigates wild-type SOD1 misfolding in Parkinson's disease using proteomics and a novel mouse model, showing mismetallation and altered post-translational modifications contribute to pathology and dopamine neuron degeneration.

Brain-derived and in vitro-seeded alpha-synuclein fibrils exhibit distinct biophysical profiles

The paper compares biophysical properties of brain-derived and in vitro-seeded alpha-synuclein fibrils from different synucleinopathies, finding structural and phosphorylation differences.

Structural basis of epitope recognition by anti-alpha synuclein antibodies MJFR14-6-4-2

The paper investigates how the antibody MJFR14-6-4-2 recognizes aggregated alpha-synuclein and shows that epitope masking and epitope concentration drive its selectivity for different aggregates.

Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?

This study investigates the association between rare SYNJ1 variants and Parkinson's disease, finding an association with both sporadic and early-onset cases.

Simulated microgravity accelerates alpha-synuclein aggregation and induces oxidative stress in an in vitro Parkinson disease model

This study shows that simulated microgravity accelerates alpha-synuclein aggregation and oxidative stress in Parkinson's disease cell models, mimicking aging-related stress.

Synaptic vesicle endocytosis deficits underlie GBA-linked cognitive dysfunction in Parkinson's disease and Dementia with Lewy bodies

This study shows that GBA mutations cause cognitive deficits in Parkinson's disease and Dementia with Lewy Bodies through synaptic vesicle endocytosis defects, independent of alpha-synuclein pathology.

α-Synuclein Strain Dynamics Predict Cognitive Transitions in Parkinson's Disease

The paper identifies distinct α-synuclein strains associated with cognitive decline in Parkinson's disease and shows AI-based analysis of these strains improves clinical stratification.

Network analysis of α-synuclein pathology progression reveals p21-activated kinases as regulators of vulnerability

The paper identifies group II p21-activated kinases as regulators of α-synucleinopathy by linking network vulnerability analysis to gene expression and pharmacological interventions.

RNA G-quadruplexes forming scaffolds for alpha-synuclein aggregation lead to progressive neurodegeneration

This study shows RNA G-quadruplexes scaffold alpha-synuclein aggregation, leading to neurodegeneration, and demonstrates that inhibiting this process can alleviate symptoms in a mouse model.

Structurally targeted mutagenesis identifies key residues supporting α-synuclein misfolding in multiple system atrophy

The paper identifies key residues in α-synuclein that support misfolding in multiple system atrophy using mutagenesis and computational modeling.

PAK6 rescues pathogenic LRRK2-mediated ciliogenesis and centrosomal cohesion defects in a mutation-specific manner

This study identifies PAK6 as a modifier of LRRK2 mutations, showing it rescues ciliogenesis defects in G2019S but not R1441C mutations.

Parkinson's Families Project: a UK-wide study of early onset and familial Parkinson's disease

The paper reports genetic findings from a UK-wide study of early-onset and familial Parkinson's disease, identifying pathogenic variants in known PD genes and highlighting the need for further monogenic causes.

Epigenetic and cognitive signatures of striatal DAT binding among healthy elderly individuals

The paper identifies epigenetic markers and cognitive associations with striatal DAT binding in healthy elderly individuals, linking them to potential early Parkinson's disease mechanisms.

Impaired Functional Connectivity of Cortico-Amygdala Pathway Can Drive Social Behavior Deficits in Synucleinopathies

This study shows that -synuclein aggregation disrupts cortico-amygdala connectivity, leading to social behavior deficits in synucleinopathies, and that restoring this connection can rescue the behavior.

Neuropathology in an α-synuclein preformed fibril mouse model occurs independent of the Parkinson's disease-linked lysosomal ATP13A2 protein

This study shows that α-synuclein pathology spreads independently of ATP13A2 in a mouse model, indicating ATP13A2 is not critical for -syn clearance or propagation.

Modelling human neuronal catecholaminergic pigmentation in rodents recapitulates age-related multisystem neurodegenerative deficits

This paper creates a transgenic mouse model that mimics human neuromelanin accumulation in catecholaminergic neurons, leading to age-related neurodegenerative deficits.

Striatal lateral inhibition regulates action selection in a mouse model of levodopa-induced dyskinesia

This study investigates how striatal lateral inhibition affects action selection in a mouse model of levodopa-induced dyskinesia, finding that altered inhibition contributes to involuntary movements.

Lead as a toxic environmental toxicant in models of synucleinopathies

This study examines how continuous and intermittent lead exposure affects synucleinopathies, finding increased aSyn inclusions and neurobehavioral impairments in animal models.

Alpha-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinsons disease

This study shows that alpha-synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons, leading to bioenergetic deficits and neuronal dysfunction in Parkinson's disease.

Tbc1d15 knockdown in vivo alleviates α-synuclein-induced neurotoxicity by promoting autophagy.

This study shows that reducing Tbc1d15 in mice enhances autophagy, reduces α-synuclein toxicity, and improves motor function in a Parkinson's disease model.

Dopamine neuron dysfunction and loss in the PrknR275W mouse model of Juvenile Parkinsonism

This study creates a PrknR275W mouse model of ARJP, showing early dopamine neuron dysfunction, age-dependent loss, and motor impairment, recapitulating key features of juvenile Parkinsonism.

RAB12-LRRK2 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes

This study identifies RAB12 as a LRRK2 substrate in mouse brains, shows its role in suppressing ciliogenesis and regulating centrosome homeostasis in astrocytes, and demonstrates that disrupting RAB12 mitigates PD-linked LRRK2 mutation effects.

Restoration of Fbxo7 expression in dopaminergic neurons restores tyrosine hydroxylase in a mouse model of Parkinson's disease

This study shows that restoring Fbxo7 expression in dopaminergic neurons of a mouse Parkinson's model rescues tyrosine hydroxylase levels in the striatum and nucleus accumbens.

Molecular signatures of altered energy metabolism and circadian rhythm perturbations in a model of extra-nigral Synucleinopathy.

This study uses spatial transcriptomics to analyze aSyn pathology in mice, revealing metabolic and circadian disruptions at different stages of disease progression.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Treated Adult Zebrafish as a Model for Parkinsons Disease

This paper develops a zebrafish model of Parkinson's Disease using MPTP treatment and reports behavioral and molecular changes resembling human PD symptoms.