Metabolomic analysis in Parkinson’s and Alzheimer’s disease.

Simple item page
dc.contributor.advisorBottiglieri, Teodoro, 1958-
dc.creatorKalecký, Karel, 1991-
dc.creator.orcid0000-0002-4212-6811
dc.date.accessioned2023-11-07T14:19:55Z
dc.date.available2023-11-07T14:19:55Z
dc.date.created2023-05
dc.date.issuedMay 2023
dc.date.submittedMay 2023
dc.date.updated2023-11-07T14:19:55Z
dc.description.abstractParkinson’s disease (PD) and Alzheimer’s disease (AD) are two most prevalent forms of neurodegeneration with progressively disabling symptoms and no cure, leading to a high burden to caregivers and society in general. The underlying disease mechanisms remain unclear and more research is required to develop novel therapies. Metabolomics is a scientific area, which explores biochemical processes happening inside an organism by measuring their intermediates. Thus, metabolomics studies the high-level functioning as also influenced by external factors including nutrition, environment, and microorganisms, directly reflecting the final phenotype. Recent technological advancements have enabled performing accurate metabolomic measurements across many pathways of metabolism simultaneously. Here, we present a series of metabolomic experiments that allows new insights into the disease mechanisms in PD and AD. Specifically, we searched for disease-related metabolic differences via case-control association studies. We focused on human brain frontal cortex and putamen, the direct location of the pathologies, combining broad investigation across many metabolic pathways with detailed analysis focused on one-carbon metabolism. Other experiments were conducted with human plasma to search for potential diagnostic biomarkers in AD and PD. Additionally, we included a mouse model of PD to compare its metabolic changes with real disease in human. The majority of experiments were targeted using liquid chromatography and flow injection analysis coupled to tandem mass spectrometry. Untargeted analysis was based on comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. Furthermore, we emphasize the importance of data processing and analysis, for which we have developed several new methods. Our results are summarized in individual chapters. The most fascinating finding implicates the anti-parkinsonian medication levodopa as a direct contributor to dementia in susceptible individuals through the accumulation of homocysteine. The susceptibility is largely explained by low amounts of betaine (trimethylglycine) and B vitamins that act as enzymatic cofactors in one-carbon metabolism, combined with specific genetic polymorphisms. Similar changes were observed in AD. The risk of developing dementia, especially in PD, could thus be potentially reduced by low-cost nutritional intervention. Collectively, our work represents a systematic effort in metabolomics in PD and AD, and constitutes a major scientific contribution in biomedical research of these diseases.
dc.format.mimetypeapplication/pdf
dc.identifier.uri
dc.identifier.urihttps://hdl.handle.net/2104/12460
dc.language.isoEnglish
dc.rights.accessrightsNo access – contact librarywebmaster@baylor.edu
dc.titleMetabolomic analysis in Parkinson’s and Alzheimer’s disease.
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentBaylor University. Institute of Biomedical Studies.
thesis.degree.grantorBaylor University
thesis.degree.namePh.D.
thesis.degree.programBiomedical Studies
thesis.degree.schoolBaylor University

Files

Original bundle

Now showing 1 - 4 of 4
No Thumbnail Available
Name:
KALECKY-PRIMARY-2023.pdf
Size:
6.22 MB
Format:
Adobe Portable Document Format
Download
No Thumbnail Available
Name:
1675375992342-Copyright Form - Signed.pdf
Size:
981.35 KB
Format:
Adobe Portable Document Format
Download
No Thumbnail Available
Name:
1679583778599-Kalecky_MDPI Open Access Information.pdf
Size:
176.51 KB
Format:
Adobe Portable Document Format
Download
No Thumbnail Available
Name:
1679583866270-Kalecky_Journal of Alzheimers Disease - IOS Press Permissions.pdf
Size:
273.74 KB
Format:
Adobe Portable Document Format
Download

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
38.47 KB
Format:
Plain Text
Description:
Download

Collections

Electronic Theses and Dissertations
Theses/Dissertations - Biomedical Studies