Parkinson's Disease Mechanisms and Treatments

Functional efficacy of the MAO-B inhibitor safinamide in murine substantia nigra pars compacta dopaminergic neurons in vitro: a comparative study with tranylcypromine

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.

Comparing alpha-synuclein-interactomes between multiple systems atrophy and Parkinsons disease reveals unique and shared pathological features.

This study compares alpha-synuclein-interactomes in multiple system atrophy and Parkinson's disease to identify unique and shared pathological features.

The Cellular and Extra-Cellular Proteomic Signature of Human Dopaminergic Neurons Carrying the LRRK2 G2019S Mutation

The paper characterizes the proteomic changes in dopaminergic neurons with the LRRK2 G2019S mutation and identifies potential biomarkers for Parkinson's disease.

Cdc25A phosphatase is activated and mediates neuronal cell death by PUMA via pRB/E2F1 pathway in a model of Parkinson's disease

Alpha-synuclein regulates the repair of genomic DNA double-strand breaks in a DNA-PKcs-dependent manner

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.

Alpha-synuclein preformed fibril-induced aggregation and dopaminergic cell death in cathepsin D overexpression and ZKSCAN3 knockout mice

This study investigates whether enhancing cathepsin D or disrupting ZKSCAN3 in the CNS can reduce α-synuclein aggregation and dopaminergic neurodegeneration, but finds no significant effect.

Viral overexpression of human alpha-synuclein in mouse substantia nigra dopamine neurons results in hyperdopaminergia but no neurodegeneration

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

Age-related decline of PKA-RIIβ level in SNc dopaminergic neurons underlies PD pathogenesis

The paper identifies a decline in PKA-RIIβ levels in SNc dopaminergic neurons of PD patients and shows that restoring PKA-RIIβ alleviates parkinsonism in mice.

Comprehensive mapping of the Interaction of levodopa and iron metabolism in Parkinson's disease

This paper uses deep machine learning to identify molecular mechanisms by which levodopa affects iron metabolism in Parkinson's disease, revealing interactions with iron transporters and pathways.

Parkinson's LRRK2-G2019S risk gene mutation drives sex-specific behavioral and cellular adaptations to chronic variable stress

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

LM11a-31 Inhibits p75 Neurotrophin Receptor (p75NTR) Cleavage and is Neuroprotective in a Cell Culture Model of Parkinson's Disease.

The paper shows that LM11a-31 inhibits p75NTR cleavage and protects neurons from oxidative stress-induced death in a Parkinson's disease model.

Alpha-synuclein-induced nigrostriatal degeneration and pramipexole treatment disrupt frontostriatal plasticity

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

Cryo-electron tomography reveals the microtubule-bound form of inactive LRRK2

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.

Intact cells selectively amplify and structurally remodel amyloid fibrils

This study shows that intact cells selectively amplify and remodel amyloid fibrils of α-synuclein, unlike in vitro or lysate systems.

Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes

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

Virally encoded single-chain antibody fragments targeting alpha-synuclein protect against motor impairments and neuropathology in a mouse model of synucleinopathy

Bradykinesia and postural instability in a model of prodromal Synucleinopathy with alpha-Synuclein aggregation in the gigantocellular nuclei.

This study induces alpha-Synuclein aggregation in the gigantocellular nuclei of transgenic mice to model prodromal Parkinson's disease and observe motor symptom progression.

Single molecule fingerprinting reveals different growth mechanisms in seed amplification assays for different polymorphs of alpha Synuclein fibrils.

The paper uses single molecule techniques to show that different alpha-synuclein polymorphs have distinct growth mechanisms in seed amplification assays, with one polymorph showing increased secondary nucleation.

Behavioral screening defines three molecular Parkinsonism subgroups in Drosophila

The paper identifies three molecular subgroups of parkinsonism in Drosophila using behavioral screening and machine learning, each linked to distinct cellular pathways.

Neuroprotection of low dose carbon monoxide in Parkinson's disease models commensurate with the reduced risk of Parkinson's among smokers

The paper shows that low-dose carbon monoxide reduces Parkinson's disease pathology in rodent models by activating HO-1, similar to the protective effect observed in smokers.

Phosphoglycerate kinase 1 is a central leverage point in Parkinson's disease driven neuronal metabolic deficits

The paper identifies PGK1 as a rate-limiting enzyme in axonal metabolism and shows its protective role against Parkinson's disease-related synaptic deficits.

Iron-sulfur cluster loss in mitochondrial CISD1 mediates PINK1 loss-of-function phenotypes

The paper shows that CISD1 dimerization in PINK1 mutants disrupts iron-sulfur cluster coordination, leading to Parkinson's disease-like phenotypes, and suggests CISD1 as a therapeutic target.

A systematic exploration of unexploited genes for oxidative stress in Parkinson's disease

The paper identifies two unexploited genes related to oxidative stress in Parkinson's disease using a pipeline to address missing data in disease-associated gene databases.

Whole-Genome Sequencing Analysis Reveals New Susceptibility Loci and Structural Variants Associated with Progressive Supranuclear Palsy

This study uses whole-genome sequencing to identify new genetic loci and structural variants associated with progressive supranuclear palsy, including novel signals in APOE and H1/H2 haplotype region variants.

Dopaminergic modulation of behavioral and electrocortical markers of interpersonal performance monitoring in Parkinson's Disease: insights from multivariate and univariate analyses

The paper examines how dopamine affects electrocortical markers of interpersonal performance monitoring in Parkinson's Disease using EEG analysis during coordination tasks with a virtual partner.

Aquaporin-4 mis-localization slows glymphatic clearance of α-synuclein and promotes α-synuclein pathology and aggregate propagation

This study shows that AQP4 mis-localization impairs glymphatic clearance of α-synuclein and promotes its aggregation and spread in neurodegenerative diseases.

Transcriptomic changes in oligodendrocytes and precursor cells predicts clinical outcomes of Parkinsons disease

The paper identifies transcriptomic changes in oligodendrocytes and precursor cells linked to Parkinson's disease outcomes and shows their predictive value for cognitive and depressive symptoms.

Residues 2-7 of alpha-synuclein regulate amyloid formation via lipid-dependent and -independent pathways

This study identifies residues 2-7 of alpha-synuclein as regulators of amyloid formation, showing they slow fibril formation and reduce aggregation in vitro and in vivo without affecting membrane binding.

Impaired neurogenesis and synaptogenesis in iPSC-derived Parkinson's patient cortical neurons with D620N VPS35 mutation

This study shows that the VPS35-D620N mutation impairs neurogenesis and synaptogenesis in iPSC-derived Parkinson's neurons, leading to synaptic dysfunction.

Network Proteomics of the Lewy Body Dementia Brain Reveals Presynaptic Signatures Distinct from Alzheimer's Disease

This study identifies distinct presynaptic protein networks in Lewy body dementia that differ from Alzheimer's disease using network proteomics.