1.Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson's disease

DOI: 10.1038/s41467-024-47552-6

https://www.nature.com/articles/s41467-024-47552-6

This study delves into the mechanism of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and its electrophysiological signature, evoked resonant neural activity (ERNA), in Parkinson's disease. They found that ERNA peaks correspond to temporally-locked neuronal inhibition in the STN, characterized its temporal dynamics, and identified a putative neural circuit involved. Moreover, ERNA was localized to the dorsal STN and its spatial relevance to DBS outcomes was assessed. The study also examined the fiber activation profile associated with ERNA. Overall, it provides insights into the neural underpinnings of DBS-mediated effects in Parkinson's disease.

2.A single-nuclei paired multiomic analysis of the human midbrain reveals age- and Parkinson's disease-associated glial changes

DOI: 10.1038/s43587-024-00583-6

https://www.nature.com/articles/s43587-024-00583-6

This study investigates the impact of aging on gene expression and chromatin accessibility in the brain, particularly in the context of Parkinson's disease (PD). By analyzing midbrain samples from young, aged, and PD postmortem individuals using single-nuclei multiomic techniques, the study reveals that all glial cell types are affected by aging, with microglia and oligodendrocytes showing further alterations in PD. Additionally, a disease-associated oligodendrocyte subtype is identified, along with genes lost over the aging and disease process, potentially predisposing healthy cells to a disease-associated phenotype. Surprisingly, chromatin accessibility remains relatively stable over aging and PD within the same cell types. However, peak-gene association patterns are substantially altered during aging and PD, indicating cell-type-specific chromosomal loci containing PD-associated single-nucleotide polymorphisms. This study sheds light on the role of oligodendrocytes in aging and PD.

3.Plasminogen degrades α-synuclein, Tau and TDP-43 and decreases dopaminergic neurodegeneration in mouse models of Parkinson's disease

DOI: 10.1038/s41598-024-59090-8

https://www.nature.com/articles/s41598-024-59090-8

This study investigates the potential therapeutic role of plasminogen in Parkinson's disease (PD). By conducting experiments in vitro, ex vivo, and in vivo using cell models and mouse models of PD, the study demonstrates that administered plasminogen crosses the blood-brain barrier, enters cells, and migrates to the nucleus. Plasminogen increases intracellular plasmin activity, binds to α-synuclein, and promotes clearance of α-synuclein, Tau, and TDP-43 proteins. Furthermore, plasminogen reduces dopaminergic neurodegeneration, increases tyrosine hydroxylase levels in key brain regions, and improves motor function in PD mouse models. These findings suggest that plasminogen has potential as a therapeutic agent for PD by exerting protective effects against neurodegeneration and protein accumulation.

4.Predictors of stress resilience in Parkinson's disease and associations with symptom progression

DOI: 10.1038/s41531-024-00692-4

https://www.nature.com/articles/s41531-024-00692-4

This study aimed to understand stress resilience in Parkinson's disease (PD) by investigating responses to the COVID-19 pandemic as a stressor. Longitudinal data from 350 PD participants were analyzed to distinguish between stressor-reactive and resilient individuals, identify resilience factors, and compare symptom progression. Results revealed two distinct groups: high stressor-reactive (123 participants) and low stressor-reactive (227 participants). Pre-existing anxiety, rumination, and non-motor symptom severity predicted high stressor-reactivity, while quality of life, social support, positive appraisal style, and cognitive abilities predicted low stressor-reactivity. Interestingly, PD-specific factors like disease duration and motor severity did not predict stressor-reactivity. Although the pandemic did not accelerate disease progression, it exacerbated depressive symptoms in stressor-reactive PD patients.

5.Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson's disease

https://www.nature.com/articles/s41598-024-54800-8

Glypicans, known biomarkers for various diseases, are increasingly implicated in neurodegenerative disorders. Glypican 4 (GPC-4), initially associated with synapse functionality, has been linked to tau hyperphosphorylation in Alzheimer's disease. However, its role in Parkinson's disease (PD) remains unclear. The scientists investigated GPC-4 levels in PD patients' biofluids (cerebrospinal fluid, serum, and tear fluid). GPC-4 expression was confirmed in all three, with highest levels in serum. Notably, GPC-4 levels correlated with cognitive decline, suggesting a role in PD-associated dementia. Additionally, PD patients with vascular risk factors showed elevated GPC-4 levels, indicating its potential as a biomarker for vascular risk stratification in PD, aiding in identifying those at higher risk of developing dementia.