Dataset Information

Microbiome and Metabolome Insights into the Role of the Gastrointestinal-Brain Axis in Parkinson's and Alzheimer's Disease: Unveiling Potential Therapeutic Targets.

ABSTRACT: Neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's disease (AD), the prevalence of which is rapidly rising due to an aging world population and westernization of lifestyles, are expected to put a strong socioeconomic burden on health systems worldwide. Clinical trials of therapies against PD and AD have only shown limited success so far. Therefore, research has extended its scope to a systems medicine point of view, with a particular focus on the gastrointestinal-brain axis as a potential main actor in disease development and progression. Microbiome and metabolome studies have already revealed important insights into disease mechanisms. Both the microbiome and metabolome can be easily manipulated by dietary and lifestyle interventions, and might thus offer novel, readily available therapeutic options to prevent the onset as well as the progression of PD and AD. This review summarizes our current knowledge on the interplay between microbiota, metabolites, and neurodegeneration along the gastrointestinal-brain axis. We further illustrate state-of-the art methods of microbiome and metabolome research as well as metabolic modeling that facilitate the identification of disease pathomechanisms. We conclude with therapeutic options to modulate microbiome composition to prevent or delay neurodegeneration and illustrate potential future research directions to fight PD and AD.

SUBMITTER: Zacharias HU

PROVIDER: S-EPMC9786685 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Microbiome and Metabolome Insights into the Role of the Gastrointestinal-Brain Axis in Parkinson's and Alzheimer's Disease: Unveiling Potential Therapeutic Targets.

Zacharias Helena U HU Kaleta Christoph C Cossais François F Schaeffer Eva E Berndt Henry H Best Lena L Dost Thomas T Glüsing Svea S Groussin Mathieu M Poyet Mathilde M Heinzel Sebastian S Bang Corinna C Siebert Leonard L Demetrowitsch Tobias T Leypoldt Frank F Adelung Rainer R Bartsch Thorsten T Bosy-Westphal Anja A Schwarz Karin K Berg Daniela D

Metabolites 20221205 12

Neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's disease (AD), the prevalence of which is rapidly rising due to an aging world population and westernization of lifestyles, are expected to put a strong socioeconomic burden on health systems worldwide. Clinical trials of therapies against PD and AD have only shown limited success so far. Therefore, research has extended its scope to a systems medicine point of view, with a particular focus on the gastrointestinal-brain axis as a ...[more]

PMID: 36557259

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Project description:Integration of omics data and deciphering the mechanism of a biological regulatory network could be a promising approach to reveal the molecular mechanism involved in the progression of complex diseases, including Alzheimer's and Parkinson's. Despite having an overlapping mechanism in the etiology of Alzheimer's disease (AD) and Parkinson's disease (PD), the exact mechanism and signaling molecules behind them are still unknown. Further, the acetylation mechanism and histone deacetylase (HDAC) enzymes provide a positive direction toward studying the shared phenomenon between AD and PD pathogenesis. For instance, increased expression of HDACs causes a decrease in protein acetylation status, resulting in decreased cognitive and memory function. Herein, we employed an integrative approach to analyze the transcriptomics data that established a potential relationship between AD and PD. Data preprocessing and analysis of four publicly available microarray datasets revealed 10 HUB proteins, namely, CDC42, CD44, FGFR1, MYO5A, NUMA1, TUBB4B, ARHGEF9, USP5, INPP5D, and NUP93, that may be involved in the shared mechanism of AD and PD pathogenesis. Further, we identified the relationship between the HUB proteins and transcription factors that could be involved in the overlapping mechanism of AD and PD. CREB1 and HINFP were the crucial regulatory transcription factors that were involved in the AD and PD crosstalk. Further, lysine acetylation sites and HDAC enzyme prediction revealed the involvement of 15 and 27 potential lysine residues of CREB1 and HINFP, respectively. Our results highlighted the importance of HDAC1(K292) and HDAC6(K330) association with CREB1 and HINFP, respectively, in the AD and PD crosstalk. However, different datasets with a large number of samples and wet lab experimentation are required to validate and pinpoint the exact role of CREB1 and HINFP in the AD and PD crosstalk. It is also possible that the different datasets may or may not affect the results due to analysis parameters. In conclusion, our study potentially highlighted the crucial proteins, transcription factors, biological pathways, lysine residues, and HDAC enzymes shared between AD and PD at the molecular level. The findings can be used to study molecular studies to identify the possible relationship in the AD-PD crosstalk.

Dataset Information

Microbiome and Metabolome Insights into the Role of the Gastrointestinal-Brain Axis in Parkinson's and Alzheimer's Disease: Unveiling Potential Therapeutic Targets.

Publications

Microbiome and Metabolome Insights into the Role of the Gastrointestinal-Brain Axis in Parkinson's and Alzheimer's Disease: Unveiling Potential Therapeutic Targets.

Similar Datasets

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