Vitamin B6, B12 and folate modulate deregulated pathways and protein aggregation in yeast model of Huntington disease

Pradhan, Sai Sanwid; Rao, Kunrui; Manjunath, Meghana; Saiswaroop, R.; Patnana, Durga Prasad; Phalguna, Kanikaram Sai; Choudhary, Bibha; Sivaramakrishnan, Venketesh

doi:10.1007/s13205-023-03525-y

Cited by 9 publications

(1 citation statement)

References 153 publications

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“…Currently, when yeast is used as a model organism, transcriptomic, proteomic, and metabolomic analyses are the most promising modern methodological approaches for understanding the molecular mechanisms of the formation of aggregates of proteins containing polyQ tracks, particularly the huntingtin protein [61][62][63][64][65].…”

Section: Polyglutamine Proteinsmentioning

confidence: 99%

Saccharomyces cerevisiae as a Model for Studying Human Neurodegenerative Disorders: Viral Capsid Protein Expression

Bayandina,

Mukha

2023

IJMS

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In this article, we briefly describe human neurodegenerative diseases (NDs) and the experimental models used to study them. The main focus is the yeast Saccharomyces cerevisiae as an experimental model used to study neurodegenerative processes. We review recent experimental data on the aggregation of human neurodegenerative disease-related proteins in yeast cells. In addition, we describe the results of studies that were designed to investigate the molecular mechanisms that underlie the aggregation of reporter proteins. The advantages and disadvantages of the experimental approaches that are currently used to study the formation of protein aggregates are described. Special attention is given to the similarity between aggregates that form as a result of protein misfolding and viral factories—special structural formations in which viral particles are formed inside virus-infected cells. A separate part of the review is devoted to our previously published study on the formation of aggregates upon expression of the insect densovirus capsid protein in yeast cells. Based on the reviewed results of studies on NDs and related protein aggregation, as well as viral protein aggregation, a new experimental model system for the study of human NDs is proposed. The core of the proposed system is a comparative transcriptomic analysis of changes in signaling pathways during the expression of viral capsid proteins in yeast cells.

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Section: Polyglutamine Proteinsmentioning

confidence: 99%

Saccharomyces cerevisiae as a Model for Studying Human Neurodegenerative Disorders: Viral Capsid Protein Expression

Bayandina,

Mukha

2023

IJMS

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Integrated Multi-Omics Analysis and Validation in Yeast Model of Amyotrophic Lateral Sclerosis

Rajaratnam,

Pradhan,

Naik

et al. 2024

Methods in Molecular Biology

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Comparative Proteomics Highlights that GenX Exposure Leads to Metabolic Defects and Inflammation in Astrocytes

Abu-Salah,

Cesur,

Anchan

et al. 2024

Environ. Sci. Technol.

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Exposure to PFAS such as GenX (HFPO dimer acid) has become increasingly common due to the replacement of older generation PFAS in manufacturing processes. While neurodegenerative and developmental effects of legacy PFAS exposure have been studied in depth, there is a limited understanding specific to the effects of GenX exposure. To investigate the effects of GenX exposure, we exposed Drosophila melanogaster to GenX and assessed the motor behavior and performed quantitative proteomics of fly brains to identify molecular changes in the brain. Additionally, metabolic network-based analysis using the iDrosophila1 model unveiled a potential link between GenX exposure and neurodegeneration. Since legacy PFAS exposure has been linked to Parkinson's disease (PD), we compared the proteome data sets between GenX-exposed flies and a fly model of PD expressing human α-synuclein. Considering the proteomic data-and network-based analyses that revealed GenX may be regulating GABA-associated pathways and the immune system, we next explored the effects of GenX on astrocytes, as astrocytes in the brain can regulate GABA. An array of assays demonstrated GenX exposure may lead to mitochondrial dysfunction and neuroinflammatory response in astrocytes, possibly linking non-cell autonomous neurodegeneration to the motor deficits associated with GenX exposure.

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Vitamin B6, B12 and folate modulate deregulated pathways and protein aggregation in yeast model of Huntington disease

Cited by 9 publications

References 153 publications

Saccharomyces cerevisiae as a Model for Studying Human Neurodegenerative Disorders: Viral Capsid Protein Expression

Saccharomyces cerevisiae as a Model for Studying Human Neurodegenerative Disorders: Viral Capsid Protein Expression

Integrated Multi-Omics Analysis and Validation in Yeast Model of Amyotrophic Lateral Sclerosis

Comparative Proteomics Highlights that GenX Exposure Leads to Metabolic Defects and Inflammation in Astrocytes

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