Article Archive

This Cell Science at a Glance article (and the accompanying poster) deliver a snapshot of the authors’ current understanding of LRRK2 function, dysfunction, and links to disease. Journal of Cell Science (2023) 136, jcs259724 (pending publication).

A STAR protocol that describes how to differentiate cryopreserved human cortical neuronal progenitors into mature cortical neurons for high-throughput imaging analysis.

Published: The KAT8 gene encodes a lysine acetyltransferase and represents the catalytically active subunit of the non-specific lethal (NSL) epigenetic remodeling complex. The authors’ study provided additional support for KAT8 inhibition as a regulator of mitophagy and autophagy processes. View original preprint. 

The authors show that this simple and intuitive filter has a dramatic effect on different types of cross-linking data ranging from individual protein complexes over medium-complexity affinity enrichments to proteome-wide cell lysates and significantly reduces the number of false-positive identifications for inter-protein links in all these types of XL-MS data.

Published: The authors’ results support previous evidence that GBA1-positive PD has a specific phenotype with more severe non-motor symptoms. However, the authors did not reproduce previous findings of more frequent prodromal PD signs in non-affected GBA1 carriers. View original preprint.

CAP-Mac is shown to have potential for non-invasive systemic gene transfer in the brains of non-human primates.

Published: This study demonstrates that the authors’ semi-automated protocol is suitable for shotgun metagenomic analysis, while allowing for a better sample treatment logistic with reduced technical variability and without compromising the structure of the oral microbiome. View original preprint.

Published: Elevated intracellular α-synuclein increases the likelihood of aggregation and conversion to toxic forms. Factors derived from bacteria induce α-synuclein accumulation in STC-1 cells. Provided support for a mechanism by which exposure of enteroendocrine cells to specific bacterial factors found in PD gut dysbiosis might facilitate accumulation, transmission of α-synuclein pathology from the gut to the brain. View original preprint.

Published: The authors’ findings define a specific molecular mechanism by which elevated levels of α-synuclein in Parkinson’s disease and related α-synucleinopathies leads to neuronal dysfunction and death. View original preprint.

Genetic modulation of P-body components alters αS toxicity, and human genetic analysis lends support to the disease-relevance of these interactions. Beyond revealing an unexpected aspect of αS function and pathology, the authors’ data highlight the versatility of conformationally plastic proteins with high intrinsic disorder.

Published: Interaction of α-syn32-46 and HLA-DRB1*15:0 is critical for gut inflammation and CD4+ T cell-mediated loss of enteric neurons in humanized mice, suggesting potential mechanisms of prodromal enteric PD.

Mutations in some of these proteins result in neurodegenerative diseases. The authors review the known properties and well-established or putative physiological roles of these proteins, and highlight the many questions that remain open about their functions.

The authors highlight emerging technological advances to respectively interrogate and model diffusion through the ECS, and point out how these may contribute in resolving the remaining enigmas of the ECS.

Published: Evidence is provided showing that intracellular aggregation of endogenous alpha-synuclein is triggered by NMel accumulation; therefore any therapeutic approach intended to decrease NMel levels may provide appealing choices for the successful implementation of novel PD therapeutics. View original preprint.

Preprint: The authors' findings indicate that tFUS treatment applied at prodromal/early disease stages provides by itself extended structural and functional preservation of the nigrostriatal pathway in neuromelanin-producing parkinsonian rats without causing overt neuronal damage.

Preprint: The authors’ data suggest that cell subtype- and synapse-specific adaptations in M1 contribute to altered cortical outputs in parkinsonism and are important aspects of PD pathophysiology.

Published: ER-PM contacts positive for VPS13A were seldomly observed in undifferentiated K562 cells, despite the presence of XK in these cells at concentrations similar to those observed after differentiation. Findings reveal the interaction of VPS13A with XK at ER-PM contacts requires a permissive state which depends upon cell type and/or functional state of the cell. View original preprint.

Published: This data show that LTCC function in DA axons, and isradipine effect, are locally governed and suggest they vary in a manner that in turn might impact on, or reflect, the cellular stress that leads to parkinsonian degeneration. View original preprint.

αSyn expression is restricted in a subset of glutamatergic synapses in BLA and its aggregation decreases cortico-BLA transmission through both gained toxicity and loss of normal function. These results might be relevant to the reduced cortical control of amygdala function that has been associated with psychiatric deficits in PD.

Preprint: Deviations from normal cluster synchronization patterns are closely associated with various malfunctions, such as neurological disorders in the brain. Here, the authors employ an open-loop control strategy, vibrational control, which does not require any state measurements. Additionally, they conduct numerical experiments to demonstrate their theoretical findings.