Parkinson's Disease Mechanisms and Treatments

Distinct alpha-synuclein strains derived from Parkinson's disease patient tissues trigger differential inclusion pathology in a novel biosensor cell model

The paper shows that distinct alpha-synuclein strains from Parkinson's disease patient tissues induce different inclusion pathologies in a biosensor cell model.

A Site-Specific Organometallic Approach for Installing Tyrosine Phosphorylation Mimics to Decipher the Role of Phosphorylation in Alpha-Synuclein (aSyn) Aggregation and Seeding

This paper introduces a site-specific organometallic method to install tyrosine phosphorylation mimics in alpha-synuclein, revealing that di- and tri-phosphorylation slow aggregation and reduce seeding activity.

Metabolic Rewiring by alpha-Synuclein Enables Mitohormetic Protection

This study shows that alpha-synuclein expression in HEK293 cells rewires metabolism to enhance mitochondrial resilience and provides protection against respiratory complex I inhibition.

Neuromodulator control of energy reserves in dopaminergic neurons

This study shows that dopamine auto receptors regulate glycogen storage in midbrain dopaminergic neurons, linking neuromodulation to metabolic resilience and vulnerability in Parkinson's disease.

State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson's disease

This study identifies state-dependent modulation of spiny projection neurons in a mouse Parkinson's model and shows how disrupting specific signaling pathways reduces levodopa-induced dyskinesia.

AI-Guided Dual Strategy for Peptide Inhibitor Design Targeting Structural Polymorphs of α-Synuclein Fibrils

This paper designs peptide inhibitors targeting α-synuclein fibril polymorphs using AI and cryo-EM data, finding two peptides that inhibit fibrillation effectively.

TMEM175, SCARB2 and CTSB associations with Parkinson's disease risk across populations.

This study identifies genetic associations between lysosomal genes and Parkinson's disease risk across diverse populations using GWAS and whole genome sequencing data.

RNA interactions drive structural and functional diversification of alpha-synuclein fibrils

This study shows RNA binding alters the structure, function, and stability of alpha-synuclein fibrils, suggesting RNA as an active co-factor in amyloid formation.

Long-read sequencing identifies FGF14 repeat expansions in Parkinson's disease

The paper identifies FGF14 GAA repeat expansions in Parkinson's disease using long-read sequencing and finds they occur in both patients and controls.

Longitudinal Proteomic Profiling Defines Robust Molecular Subtypes Underlying the Heterogeneity of Parkinson's Disease

The paper uses longitudinal proteomic data to identify molecular subtypes of Parkinson's disease, revealing conserved modules and their associations with clinical phenotypes.

Cellular and Extracellular microRNA Dysregulation in LRRK2-Linked Parkinson's Disease

This study identifies differentially expressed micro-RNAs in LRRK2 G2019S mutation carriers using induced pluripotent stem cell-derived neurons, showing no linear correlation with LRRK2 activity.

Soluble Immune Factor Profiles in Blood and CSF Associated with LRRK2 Mutations and Parkinson's Disease

This study identifies immune factor profiles in blood and CSF associated with LRRK2 mutations and Parkinson's disease, showing distinct changes in serum and CSF markers.

Surface Wetting Is a Key Determinant of α-Synuclein Condensate Maturation

This study investigates how N-terminal truncation and surface wetting influence α-synuclein condensate maturation and suggests a mechanism linking surface interactions to toxic aggregate formation.

Multi-Omic Analysis Reveals Lipid Dysregulation Associated with Mitochondrial Dysfunction in Parkinson's Disease Brain

This study identifies lipid dysregulation linked to mitochondrial dysfunction in Parkinson's Disease brain regions through multi-omics analysis of lipids, proteomics, and mitochondrial activity.

Age-Dependent Effects of Paraquat-Induced Parkinsonism on Serum Alpha-Synuclein Expression, Substantia Nigra Histoarchitecture and Neurobehaviour in Male Wistar Rats

This study examines age-dependent effects of paraquat-induced Parkinsonism on serum alpha-synuclein, substantia nigra structure, and neurobehavior in male rats, finding greater vulnerability in adults.

Formation of Condition-Dependent Alpha-Synuclein Fibril Strain in Artificial Cerebrospinal Fluid

This study shows that artificial cerebrospinal fluid (aCSF) forms distinct aSyn fibrils with unique structural features that change when key CSF components are removed.

Lipid droplets promote the aberrant liquid-liquid phase separation of alpha-synuclein leading to impaired energy homeostasis

This study shows lipid droplets promote alpha-synuclein phase separation, leading to mitochondrial toxicity and neurodegeneration in Parkinson's disease.

ClC-7 links PIKfyve inhibition to Rab-dependent LRRK2 activity at lysosomes

This study shows that PIKfyve inhibition enhances LRRK2 signaling via ClC-7-dependent lysosomal remodeling and Rab accumulation, revealing distinct Rab and GABARAP inputs for LRRK2 activation under different lysosomal stresses.

Controlling interfacial protein adsorption, desorption and aggregation in biomolecular condensates

This study investigates how amyloidogenic proteins like synuclein adsorb to biomolecular condensates and how this process can be modulated to slow aggregation.

Scalable Human Cellular Models of Parkinson Disease Reveal A Druggable Link Between the Angiotensin Receptor 1 and Alpha-Synuclein Pathology

This study uses human iPSC-derived models to show AGTR1 inhibition protects mDA neurons from degeneration and reduces alpha-synuclein pathology.

Deletion or Targeted Blockade of FcγRIIb (CD32b) Impairs α-Syn Propagation In-Vivo

This study shows that FcγRIIb promotes α-syn propagation and neurotoxicity in vivo, suggesting it as a therapeutic target for synucleinopathies.

Explainable 3D CNNs link regional and network level disruption in early Parkinson's MRIs to symptom progression

This study uses explainable 3D CNNs to identify regional and network-level biomarkers in early Parkinson's MRIs linked to symptom progression.

A Load-Induced Energetic Tipping Point Explains Selective Vulnerability of Substantia Nigra Neurons

The paper develops a minimal energetic model to explain why SNc neurons are more vulnerable than VTA neurons in Parkinson's disease, showing that load-induced bistability leads to irreversible collapse under stress.

CHCHD2 mutant mice display mitochondrial protein accumulation and disrupted energy metabolism

This study generates CHCHD2 T61I mutant mice to model Parkinson's disease, finding mitochondrial dysfunction and metabolic shifts towards glycolysis.

Thermodynamic Stability Modulates Chaperone-Mediated Disaggregation of α-Synuclein Fibrils

This study shows that the thermodynamic stability of alpha-synuclein fibrils affects their disaggregation by the chaperone system HSP70, DNAJB1, and Apg2, with more stable fibrils being less efficiently disaggregated.

Sex-specific trajectories of gait adaptation following partial dopaminergic lesions in a rat model of parkinsons disease

This study examines sex-specific gait adaptation in rats with partial dopaminergic lesions, revealing differences in motor recovery trajectories between males and females.

MOLECULAR ANALYSIS OF MITOCHONDRIAL COMPLEX I IN THE RESPONSIVENESS TO LEVODOPA IN PARKINSON'S DISEASE

This study identifies mitochondrial DNA variants associated with levodopa responsiveness in Parkinson's disease patients, highlighting specific subunit mutations and population-specific variants.

Co-infection with two α-synuclein strains reveals novel synergistic interactions

This study investigates co-infection with two α-synuclein strains in mice, finding synergistic interactions that accelerate disease progression.

iPSC derived MSC secretome activates distinct neuroprotective pathways in a preclinical model of Parkinsons disease

The paper compares the neuroprotective effects of bone marrow MSCs and iPSC-derived MSCs secretomes in a Parkinson's disease model, finding that iMSCs secretome better preserves dopaminergic neurons and activates broader protective pathways.

Parkinsons disease modeling in regenerative spiny mice (Acomys dimidiatus) captures key disease-relevant behavioral, histological, and molecular signatures

This study models Parkinson's disease in spiny mice, showing they exhibit key disease features like behavioral impairments, neuronal degeneration, and proteomic changes similar to PD.