Article Archive

The app features interactive frequency tables that globally summarize both the original UniProtKB input query as well as the extracted/changed entry values. Moreover, UniProtExtractR includes a tractable mapping algorithm to define custom organelle-level resolution.

During nutrient stress, macroautophagy is employed to degrade cellular macromolecules, thereby providing biosynthetic building blocks while simultaneously remodeling the proteome. The authors' results, available via an interactive web tool, reveal that autophagic turnover prioritizes membrane-bound organelles (principally Golgi and ER) for proteome remodeling during nutrient stress.

Preprint: The class III phosphatidylinositol (PI) 3-kinase complexes I and II (PI3KC3-C1 and -C2) are central to the initiation of macroautophagy and endosomal maturation, respectively. These results provide a pathway of general mechanism for PI3KC3 activation in autophagy and endosome biogenesis and a roadmap for their pharmacological upregulation.

Preprint: The authors'results thus define NAP1 and SINTBAD as cargo receptor rheostats, elevating the threshold for mitophagy initiation by OPTN while promoting the progression of the pathway once set in motion by supporting NDP52. These findings shed light on the cellular strategy to prevent pathway hyperactivity while still ensuring efficient progression.

Preprint: In the present study, the authors exploited the SH-SY5Y cell model overexpressing a pro-aggregation form of alpha-synuclein to investigate the efficacy of PIKfyve-mediated lysosomal biogenesis, through TFEB, as a potential target for Parkinson's therapy.

Perspective on the biochemical consequences of glucocerebrosidase 1 mutations in Parkinson’s disease.

The asymmetry between striatal and SNc changes for both dopaminergic depletion and microstructural degeneration biomarkers are consistent with a neurodegenerative process that begins in the striatal terminals before progressing toward the cell bodies in the SNc.

This study demonstrates that the authors' semi-automated protocol is suitable for shotgun metagenomic analysis, by significantly producing higher DNA fragment sizes while allowing for improved sample treatment logistics with reduced technical variability and without compromising the structure of the oral microbiome.

Published: Many natural and man-made network systems need to maintain certain patterns, such as working at equilibria or limit cycles, to function properly. The authors provide some numerical results that demonstrate the validity of our theoretical findings.

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.

Published: 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. View original preprint.

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.

Published: 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. View original preprint.

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.

Published: 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. View original preprint.

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.