Dataset Information

Microbiota-Derived β-Amyloid-like Peptides Trigger Alzheimer's Disease-Related Pathways in the SH-SY5Y Neural Cell Line.

ABSTRACT: Here, we present the first in silico and in vitro evidence of Aβ-like peptides released from meaningful members of the gut microbiome (mostly from the Clostridiales order). Two peptides with high homology to the human Aβ peptide domain were synthesized and tested in vitro in a neuron cell-line model. Gene expression profile analysis showed that one of them induced whole gene pathways related to AD, opening the way to translational approaches to assess whether gut microbiota-derived peptides might be implicated in the neurodegenerative processes related to AD. This exploratory work opens the path to new approaches for understanding the relationship between the gut microbiome and the triggering of potential molecular events leading to AD. As microbiota can be modified using diet, tools for precise nutritional intervention or targeted microbiota modification in animal models might help us to understand the individual roles of gut bacteria releasing Aβ-like peptides and therefore their contribution to this progressive disease.

SUBMITTER: Blanco-Miguez A

PROVIDER: S-EPMC8624230 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Microbiota-Derived β-Amyloid-like Peptides Trigger Alzheimer's Disease-Related Pathways in the SH-SY5Y Neural Cell Line.

Blanco-Míguez Aitor A Tamés Hector H Ruas-Madiedo Patricia P Sánchez Borja B

Nutrients 20211029 11

Here, we present the first in silico and in vitro evidence of Aβ-like peptides released from meaningful members of the gut microbiome (mostly from the Clostridiales order). Two peptides with high homology to the human Aβ peptide domain were synthesized and tested in vitro in a neuron cell-line model. Gene expression profile analysis showed that one of them induced whole gene pathways related to AD, opening the way to translational approaches to assess whether gut microbiota-derived peptides migh ...[more]

PMID: 34836123

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Project description:Peptides have revealed a large range of biological activities with high selectivity and efficiency for the development of new drugs, including neuroprotective agents. Therefore, this work investigates the neuroprotective properties of naturally occurring peptides, endomorphin-1 (EM-1), endomorphin-2 (EM-2), rubiscolin-5 (R-5), and rubiscolin-6 (R-6). We aimed at answering the question of whether well-known opioid peptides can counteract cell injury in a common in vitro model of Parkinson's disease (PD). Antioxidant activity of these four peptides was evaluated by the 2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging activity, oxygen radical absorbance capacity (ORAC), and ferric-reducing antioxidant power (FRAP) assays, while neuroprotective effects were assessed in a neurotoxic model induced by 6-hydroxydopamine (6-OHDA) in a human neuroblastoma cell line (SH-SY5Y). The mechanisms associated with neuroprotection were investigated by the determination of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, and Caspase-3 activity. Among the tested peptides, endomorphins significantly prevented neuronal death induced by 6-OHDA treatment, decreasing MMP (EM-1) or Caspase-3 activity (EM-2). Meanwhile, R-6 showed antioxidant potential by FRAP assay and exhibited the highest capacity to recover the neurotoxicity induced by 6-OHDA via attenuation of ROS levels and mitochondrial dysfunction. Generally, we hypothesize that peptides' ability to suppress the toxic effect induced by 6-OHDA may be mediated by different cellular mechanisms. The protective effect caused by endomorphins results in an antiapoptotic effect (mitochondrial protection and decrease in Caspase-3 activity), while R-6 potency to increase a cell's viability seems to be mediated by reducing oxidative stress. Our results may provide new insight into neurodegeneration and support the short peptides as a potent drug candidate to treat PD. However, further studies should be conducted on the detailed mechanisms of how tested peptides could suppress neuronal injuries.

Dataset Information

Microbiota-Derived β-Amyloid-like Peptides Trigger Alzheimer's Disease-Related Pathways in the SH-SY5Y Neural Cell Line.

Publications

Microbiota-Derived β-Amyloid-like Peptides Trigger Alzheimer's Disease-Related Pathways in the SH-SY5Y Neural Cell Line.

Similar Datasets

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