Parkinson's Disease Mechanisms and Treatments

This study shows that nigrostriatal degeneration and pramipexole differentially impair behavioural flexibility in rats, with effects dependent on premorbid behavioural flexibility.

The paper identifies genes critical for dopaminergic neuron development and differentiation that are downregulated in Parkinson's disease and shows their role in disease progression.

The paper shows that alpha-synuclein oligomers activate NFAT, leading to neuronal toxicity and synaptic loss, which can be reversed by NFAT inhibitors.

This study shows nicotine promotes GABAergic neurons to adopt a dopaminergic phenotype, reducing alpha-synuclein-induced motor deficits in Parkinson's models.

This study analyzes codon usage patterns in Parkin protein mutations associated with Parkinsonism and finds significant disease associations with mutations at the first two codon positions.

This study shows that mutations in synaptojanin1 and auxilin synergistically worsen dopaminergic axonal pathology in mice, suggesting a role in Parkinson's disease pathogenesis.

This study identifies MTK458, a PINK1 activator, which reduces α-synuclein pathology and pUb levels in Parkinson's disease models and correlates plasma pUb with disease progression.

The paper screens a Turkish dementia cohort for VCP variants and identifies a missense variant associated with prodromal dementia with Lewy bodies.

This study identifies parieto-temporo-occipital cortical volume loss in Parkinson's Disease psychosis and links it to serotonergic receptor gene expression.

This study shows that UBA52 interacts with VDAC1 to prevent mitochondrial dysfunction and dopaminergic neuronal death in Parkinson's disease.

This study identifies TNK2 as a regulator of dopamine and epigenetic processes in Parkinson's disease, showing that mutations in TNK2 affect neuroprotection through interactions with RNAi and dopamine transport.

The paper presents a multi-layered molecular dataset from iPSC-derived dopaminergic neurons to model Parkinson's disease genetic risk and provides a data browser for accessing these resources.

The paper identifies translational repression of proteostasis regulators in fibroblasts from both sporadic and LRRK2-G2019S Parkinson's patients using proteomics.

This study shows insulin signaling modulates AMPK activity to regulate Pink1 mRNA localization, affecting PINK1 function in neurons and linking insulin resistance to mitochondrial dysfunction.

The paper conducts an X-chromosome association study in Latin American cohorts, identifying new loci linked to Parkinson Disease and replicating previous findings.

This study uses CRISPRi to downregulate alpha-synuclein in a Parkinson's disease patient-derived model, reducing oxidative stress and mtDNA damage.

This study identifies nonmotor symptoms linked to early dopaminergic neuron loss in a mouse Parkinson's disease model.

This study identifies β-spectrin as a key binding partner of α-synuclein, showing that their interaction disrupts the spectrin-ankyrin complex, leading to neuronal dysfunction and death in Parkinson's disease and related disorders.

This study compares dopamine neuron phenotypes from PD patients with mutations in GBAN370S and LRRK2G2019S to engineered SNCAA53T iPSC-derived neurons, revealing divergent pathogenic mechanisms and potential therapeutic targets.

This study investigates olfactory dysfunction in a mouse model of Parkinson's disease, finding that alpha-synuclein pathology and reduced neurogenesis in the olfactory bulb contribute to impaired olfaction.

This study examines how a mitochondrial polygenic score interacts with environmental factors to influence age at onset in LRRK2-PD and iPD, finding ethnic-specific effects and gene-environment interactions.

This study shows bacterial ligands and metabolites increase α-synuclein levels in gut enteroendocrine cells, potentially contributing to Parkinson's disease pathology.

This study identifies vincamine as a potential therapeutic for Parkinson's disease by showing it reduces oxidative stress and motor defects in Drosophila and human cell models.

This study shows that low-dose rotenone given after colitis worsens gut dysfunction and accelerates dopaminergic neuron loss in a mouse model of Parkinson's disease.

This study shows that genetic inactivation of USP19 reduces a-synuclein ubiquitination and Lewy body-like aggregate accumulation in a mouse model of Parkinson's disease.

This study shows that extracellular alpha-synuclein toxicity in Parkinson's disease is independent of intracellular alpha-synuclein and linked to mitochondrial dysfunction.

This study uses machine learning to identify Parkinson's disease subtypes and predict progression in two cohorts, finding three subtypes with distinct progression rates and high prediction accuracy.

The paper identifies SGC0946, a DOT1L inhibitor, as a candidate molecule that enhances dopaminergic neuron survival in vitro through a high-throughput screening approach.

The paper identifies mitochondrial DNA heteroplasmy as a marker distinguishing disease manifestation in PINK1/PRKN mutation carriers.