Article Archive

Preprint: Breach of lysosomes allows mtDNA to access cytosol, requiring multiple Parkinson's disease-related proteins and Gasdermin pores, identified in the screen. These data place mitochondria-to-lysosome transport as a driver of pyroptosis and link multiple PD proteins along a common pathway.

Published: Based on a functional annotation analysis on chromosome 1, we determined that changes in DNAJB4 gene expression, close to LRP8, are an additional potential cause of increased susceptibility to LiD. Baseline anxiety status was significantly associated with LiD.

Published: The molecular signals driving varied pathways are discussed, including the cellular and physiological contexts under which the different degradation pathways are engaged.

Preprint: Structural and functional data support a model in which the TBK1-dependent phosphorylation of RAB7A serves as a switch, promoting mitophagy by relieving Rubicon inhibition and favoring Pacer activation.

Published: Multiple lines of evidence suggest that Ptbp1 depletion can convert a selective subpopulation of glial cells into neurons and, via this and other mechanisms, reverse deficits in a Parkinson's disease model, emphasizing the importance of future efforts in exploring this therapeutic strategy. 

Published: Over 15 FDA approved drugs, numerous ongoing clinical trials, RNA therapeutics, such as small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs), have shown potential to treat human disease. RNA therapeutics can be used to treat widespread human disease, the rate-limiting delivery problem of endosomal escape must be solved in a nontoxic manner.

Preprint: Like a handful of other neuronal types in the brain, cholinergic neurons (CNs) in the pedunculopontine nucleus (PPN) are lost in the course of Parkinson’s disease (PD). PPN CNs have a distinctive physiological phenotype that shares some, but not all, of the features of other neurons that are selectively vulnerable in PD.

Preprint: Loss-of-function variants in ATP13A2 are causative for Kufor-Rakeb syndrome (KRS, a recessive juvenile-onset parkinsonism with dementia) and also identified in early-onset PD (EOPD) and hereditary spastic paraplegia (HSP). The ALS and MSA variants presented a subtle functional defect, questioning whether these heterozygous variants are pathogenic and ATP13A2 dysfunction may cause MSA or ALS.

Compounds enhancing lysosomal function broadly ameliorate AD-associated pathologies. The authors’ findings establish cell-autonomous LQC dysfunction in neurons as a central vulnerability in aging and AD pathogenesis.

Preprint: These results suggest that the limited efficiency of autophagy in clearing polyQ aggregates is due to the inability of autophagosomes to interact productively with the non-deformable, fibrillar disease aggregates.

Preprint: Gain-of-function mutations in the LRRK2 gene cause Parkinson’s disease (PD), characterized by debilitating motor and non-motor symptoms. The authors’ results reveal a mechanism by which pathogenic hyperactive LRRK2 may contribute to the altered synaptic homeostasis associated with characteristic non-motor and cognitive manifestations of PD.

In a near-complete pathway from the initial membrane recruitment to the LC3 lipidation reaction, the three-step targeting of the ATG12--ATG5-ATG16L1 machinery establishes a high level of regulatory control.

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.

Preprint: 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.

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.

Preprint: 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.

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

Preprint: 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.

Preprint: 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.