Parkinson's Disease Mechanisms and Treatments

PD-linked LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance via ERM hyperphosphorylation

This study shows that the LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance by hyperphosphorylating ERM proteins, which disrupts the Ezrin/Atg7 interaction and autophagy.

Exploring the Genetic and Genomic Connection Underlying Neurodegeneration with Brain Iron Accumulation and the Risk for Parkinson's Disease

This study investigates the genetic and genomic links between NBIA and PD, finding no strong association and suggesting they may be distinct conditions.

α-synuclein preformed fibrils bind to β-neurexins and impair β-neurexin-mediated presynaptic organization

This study identifies β-neurexins as presynaptic proteins that bind to α-synuclein preformed fibrils, impairing presynaptic organization and contributing to synucleinopathy pathology.

The role of microglial LRRK2 in manganese-induced inflammatory neurotoxicity via NLRP3 inflammasome and RAB10-mediated autophagy dysfunction

This study investigates how manganese exposure increases microglial LRRK2 activity, leading to neuroinflammation and toxicity, with exacerbation in LRRK2 G2019S mutation.

Distribution of phosphorylated alpha-synuclein in non-diseased brain implicates olfactory bulb mitral cells in synucleinopathy pathogenesis

The paper identifies PSER129 accumulation in healthy olfactory bulb mitral cells and links it to synucleinopathy pathogenesis through protein interactome analysis.

Post-fibrillization nitration of alpha-synuclein abolishes its seeding activity and pathology formation in primary neurons and in vivo

This study shows that nitration of alpha-synuclein after fibrillization reduces its seeding activity and pathology formation in neurons and in vivo.

The utility and caveat of split-GAL4s in the study of neurodegeneration

The paper identifies vulnerable DA neuron subpopulations in Drosophila PD models using split-GAL4 and highlights an age-related caveat of the system.

Nigral Transcriptomic Profiles in Engrailed-1 Hemizygous Mouse Models of Parkinson's Disease Reveal Upregulation of Oxidative Phosphorylation-Related Genes Associated with Resistance to Dopaminergic Neurodegeneration

This paper compares transcriptomic profiles in En1-hemizygous mice to identify gene expression differences linked to susceptibility to Parkinson's-like neurodegeneration.

Neuronal identity defines a-synuclein and tau toxicity

The paper identifies molecular signatures of neuronal vulnerability to α-synuclein and tau toxicity, showing differential susceptibility independent of expression levels.

Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus

This study shows that tyrosinase-induced neuromelanin accumulation in mouse locus coeruleus neurons causes hyperactivity, transcriptional changes, and degeneration, mimicking early stages of Alzheimer's and Parkinson's disease.

Brain-wide transcriptome-based metabolic alterations in Parkinsons disease: human inter-region and human-experimental model correlations

The paper identifies metabolic alterations in Parkinson's disease using human brain transcriptomes and experimental models, finding regional correlations and heterogeneity in metabolic pathways.

Classification of Parkinson's Disease and Delineating Progression Markers from the Sebum Volatilome

This study identifies volatile compounds in sebum that differentiate Parkinson's Disease and REM sleep behaviour disorder, showing changes over disease progression.

Dopamine transporter and synaptic vesicle sorting defects initiate auxilin-linked Parkinson's disease

This study shows that auxilin deficiency causes Parkinson's disease by disrupting dopamine transporter function and synaptic vesicle sorting, leading to dopamine homeostasis disruption and neurodegeneration.

Premorbid performances determine the deleterious effects of nigrostriatal degeneration and pramipexole on behavioural flexibility

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

Genes critical for development and differentiation of dopaminergic neurons are downregulated in Parkinson's disease

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.

Alpha-synuclein oligomers activate nuclear factor of activated T-cells (NFAT) modulating apoptosis and synaptic homeostasis

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

Nicotine-mediated recruitment of GABAergic neurons to a dopaminergic phenotype attenuates motor deficits in alpha-synuclein Parkinson's model.

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

Comprehensive codon usage analyses of the mutations in the Parkin protein leading to Parkinsonism

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.

Mutations in Parkinsonism-linked endocytic proteins synaptojanin1 and auxilin have synergistic effects on dopaminergic axonal pathology

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

Pharmacological PINK1 activation ameliorates Pathology in Parkinson's Disease models

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.

Genetic analysis of VCP variants in a Turkish dementia cohort

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

Neuroanatomical substrates in Parkinson's Disease psychosis and their association with serotonergic receptor gene expression: A coordinate-based meta-regression analysis.

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

UBA52 attunes VDAC1-mediated mitochondrial dysfunction and dopaminergic neuronal death

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

Integrated Regulation of Dopaminergic and Epigenetic Effectors of Neuroprotection in Parkinson's Disease Models

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 Foundational data initiative for Parkinsons disease (FOUNDIN-PD): enabling efficient translation from genetic maps to mechanism

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.

Regulators of proteostasis are translationally repressed in fibroblasts from sporadic and LRRK2-G2019S Parkinson's patients

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

Insulin signaling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons

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.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease

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

Nuclease-dead S. aureus Cas9 downregulates alpha-synuclein and reduces mtDNA damage and oxidative stress levels in patient-derived stem cell model of Parkinson's disease

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

Nonmotor symptoms associated with progressive loss of dopaminergic neurons in a mouse model of Parkinson's disease

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