Parkinson's Disease Mechanisms and Treatments

This study shows high-dose levodopa impairs lysosomal function and reduces lysosomal acidity in sensory neurons, independent of homocysteine effects.

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.

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

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.

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.

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

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.

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

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.

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

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

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.

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.

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.

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

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.

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.

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.

This study shows that targeting CB2 with SMM-189 reduces alpha-synuclein aggregates and neuroinflammation in a rat model of Parkinson's disease.

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

This study compares the effects of safinamide and tranylcypromine on dopamine signaling in SNpc dopaminergic neurons, finding that safinamide only mildly prolongs DA-mediated firing inhibition.

This study shows that alpha-synuclein regulates DNA double-strand break repair via DNA-PKcs in HAP1 cells and neurons, linking its dysfunction to genomic instability in neurodegenerative diseases.

This study overexpresses human alpha-synuclein in mouse dopamine neurons and finds increased dopamine levels and activity without neurodegeneration.

This study investigates how the LRRK2-G2019S mutation affects sex-specific anxiety-like behaviors and neural activity in response to chronic stress in mice.

This study examines how nigrostriatal degeneration and pramipexole treatment affect frontostriatal plasticity and synaptic markers in rats.

This study uses computational methods to analyze the binding of PRX002 to alpha-synuclein, showing strong binding affinity and conformational stability.

This study uses cryo-ET to show that LRRK2 can form microtubule-bound filaments in its autoinhibited state, with structural differences compared to active-LRRK2 filaments.

This study identifies six genetic loci associated with progressive supranuclear palsy, including a novel locus, and links them to oligodendrocytic dysfunction and C4A expression.