Dataset Information

PIN1 Modulates Huntingtin Levels and Aggregate Accumulation: An In vitro Model.

ABSTRACT: Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by a polyglutamine expansion within the N-terminal region of huntingtin protein (HTT). Cellular mechanisms promoting mutant huntingtin (mHTT) clearance are of great interest in HD pathology as they can lower the level of the mutant protein and its toxic aggregated species, thus affecting disease onset and progression. We have previously shown that the prolyl-isomerase PIN1 represents a promising negative regulator of mHTT aggregate accumulation using a genetically precise HD mouse model, namely HdhQ111 mice. Therefore, the current study aims at underpinning the mechanism by which PIN1 affects huntingtin's aggregates. We found that PIN1 overexpression led to a reduction of mHTT aggregates in HEK293 cells, and that this could be linked to a negative regulation of mHTT half-life by PIN1. Furthermore, we show that PIN1 has the ability to stimulate the proteasome presenting evidence of a mechanism regulating this phenomenon. Our findings provide a rationale for future investigation into PIN1 with the potential for the development of novel therapeutic strategies.

SUBMITTER: Carnemolla A

PROVIDER: S-EPMC5420564 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PIN1 Modulates Huntingtin Levels and Aggregate Accumulation: An <i>In vitro</i> Model.

Carnemolla Alisia A Michelazzi Silvia S Agostoni Elena E

Frontiers in cellular neuroscience 20170508

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by a polyglutamine expansion within the N-terminal region of huntingtin protein (HTT). Cellular mechanisms promoting mutant huntingtin (mHTT) clearance are of great interest in HD pathology as they can lower the level of the mutant protein and its toxic aggregated species, thus affecting disease onset and progression. We have previously shown that the prolyl-isomerase PIN1 represents a promising negative ...[more]

PMID: 28533744

Similar Datasets

Project description:Soil aggregates contain distinct physio-chemical properties across different size classes. These differences in micro-habitats support varied microbial communities and modulate the effect of plant on microbiome, which affect soil functions such as disease suppression. However, little is known about how the residents of different soil aggregate size classes are impacted by plants throughout their growth stages. Here, we examined how tomato plants impact soil aggregation and bacterial communities within different soil aggregate size classes. Moreover, we investigated whether aggregate size impacts the distribution of soil pathogen and their potential inhibitors. We collected samples from different tomato growth stages: before-planting, seedling, flowering, and fruiting stage. We measured bacterial density, community composition, and pathogen abundance using qPCR and 16 S rRNA gene sequencing. We found the development of tomato growth stages negatively impacted root-adhering soil aggregation, with a gradual decrease of large macro-aggregates (1-2 mm) and an increase of micro-aggregates (<0.25 mm). Additionally, changes in bacterial density and community composition varied across soil aggregate size classes. Furthermore, the pathogen exhibited a preference to micro-aggregates, while macro-aggregates hold a higher abundance of potential pathogen-inhibiting taxa and predicted antibiotic-associated genes. Our results indicate that the impacts of tomatoes on soil differ for different soil aggregate size classes throughout different plant growth stages, and plant pathogens and their potential inhibitors have different habitats within soil aggregate size classes. These findings highlight the importance of fine-scale heterogeneity of soil aggregate size classes in research on microbial ecology and agricultural sustainability, further research focuses on soil aggregates level could help identify candidate tax involved in suppressing pathogens in the virtual micro-habitats.

Dataset Information

PIN1 Modulates Huntingtin Levels and Aggregate Accumulation: An In vitro Model.

Publications

PIN1 Modulates Huntingtin Levels and Aggregate Accumulation: An <i>In vitro</i> Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets