Article Archive

Parkinson's disease (PD) involves dysregulated neuroimmune crosstalk and gut-brain axis inflammation. Gastrointestinal dysfunction is a common early symptom. Iron dysregulation and immune cell dysfunction may play a role, with shared features in PD an IBD.

The authors created a new collection of 24 genetically well-controlled Drosophila models of familial forms of Parkinsonism. Using unbiased behavioral screening and machine learning, they identified three clusters of mutants that converge.

Using a reporter mouse line expressing tdTomato under control of DAT promoter in the gut and single cell sequencing, the authors uncovered a novel population of DA neurons unique to the ENS which was ChAT/DAT-tdTomato-immunoreactive and expressed Grp, Calcb.

This book chapter will be published (open-access) in October 2024. Book title: Translational Methods for Parkinson’s Disease and Atypical Parkinsonism Research. Editors: Sergiu Groppa, Susanne Schneider.

Synucleinopathies like Parkinson’s disease dementia are linked to cognitive impairments due to Lewy bodies. Various methods, like genetic manipulation and toxin exposure, can model these pathologies in research to understand human diseases better.

During selective autophagy transmembrane, cargo receptors can trigger autophagy by recruiting different complexes and utilizing multiple pathways. This flexibility in autophagy initiation has important therapeutic implications.

PD and DLB involve α-syn inclusions in the amygdala affecting cognition and emotions. Cortico-amygdala synapses with α-syn aggregates show increased volume of synapses, potentially contributing to behavioral impairments.

The intraputaminal delivery of AAV9-SynA53T resulted in a widespread synucleinopathy throughout the cerebral cortex and substantia nigra in the non-human primate brain.

GEARBOCS is a non-invasive method for precise gene editing in astrocytes using CRISPR/Cas9. It allows knockout, tagging, and reporter knock-in strategies, revealing the roles of Sparcl1 and Vamp2 in synapse maintenance in the mouse visual cortex.

This study of MPTP-induced Parkinsonism in macaques indicates that changes in the timing of task-related neural activity of the internal segment of the globus pallidus (GPi) correlate with the severity of motor impairments.

High-resolution connectomics in human participants provides evidence for a non-canonical circuit linking the limbic ventral putamen to the motor cortex. The data is in line with previous findings in nonhuman primates.

Safinamide (SAF) is used for PD by enhancing dopamine signal. SAF prolongs recovery from dopamine-mediated firing inhibition in SNpc DAergic neurons, mildly compared to tranylcypromine, suggesting multiple sites of action for SAF's therapeutics.

Lysosomal and mitochondrial dysfunction are implicated in many diseases. GEM-SCOPe, a modular toolbox of fluorescent markers, helps visualize these organelles. In a PRKN-knockout model of PD, GEM-SCOPe identified disease-associated changes.

The authors systematically investigated experimental and computational design choices for their effects on allelic imbalance analysis in droplet-based snRNA-seq data from human samples. They also show many factors including read length and sequencing technology.

Reduced olfaction is a common feature of typical Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The authors created a simplified smell test based on seven specific odorants that can distinguish PD/DLB patients from healthy controls.

Perspective article on the publication (Chen et al. (2023), Sci Adv). It summarizes the major findings of this research paper and highlights a few potential future directions regarding the motor cortical circuit changes in Parkinsonism.

This paper discusses cellular senescence as a therapeutic target in aging and age-related diseases, as well as strategies and recent advances in the development of senotherapeutics targeting senescent cells to treat age-related diseases.

nMOST workflow quantifies proteomes and lipidomes in LSD mutants, identifying diverse molecular phenotypes. NPC2-/- cells show ferritinophagy defects leading to mitochondrial issues, resolved with iron supplementation.

This article reviews the role of cortico-basal ganglia circuits in speech motor learning and execution in Parkinson's disease.

The results documented motor cortical neuronal hyperexcitability associated with αSyn aggregation and provided a novel mechanistic understanding of cortical circuit dysfunction in PD.