Advances of Mechanisms-Related Metabolomics in Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a multifactorial disorder characterized by progressively debilitating dopaminergic neurodegeneration in the substantia nigra and the striatum, along with various metabolic dysfunctions and molecular abnormalities. Metabolomics is an emerging study and has been demonstrated to play important roles in describing complex human diseases by integrating endogenous and exogenous sources of alterations. Recently, an increasing amount of research has shown that metabolomics profiling holds great promise in providing unique insights into molecular pathogenesis and could be helpful in identifying candidate biomarkers for clinical detection and therapies of PD. In this review, we briefly summarize recent findings and analyze the application of molecular metabolomics in familial and sporadic PD from genetic mutations, mitochondrial dysfunction, and dysbacteriosis. We also review metabolic biomarkers to assess the functional stage and improve therapeutic strategies to postpone or hinder the disease progression.

Peripheral metabolic alterations associated with pathological manifestations of Parkinson’s disease in gut-brain axis-based mouse model

“…However, in the case of PD patients, since most of the cases of taking drugs such as levodopa can affect the metabolites, it may not be established whether pathological changes can be reflected ( Gonzalez-Riano et al, 2021 ; Gatarek et al, 2022 ). In the case of mouse models, although variously known, changes in lipid-based metabolomes and bile acid synthesis-related metabolomes were found to be effective ( Graham et al, 2018 ; Zhang Y. et al, 2021 ). The difference between the mouse model shown in previous reports and the results of this study needs to be further compared through additional analysis.…”

“…Metabolites related to sugar metabolism are also correlated with the intestinal pathological phenotypes. In particular, as there are several reports that intestinal barrier dysfunction is aggravated when the amount of glucose is increased or when the state of hyperglycemia is present (Thaiss et al, 2018;Zhang X. et al, 2021), changes in related metabolites may have also affected the action of intestinal pathology (Supplementary Figure S2). Therefore, it is highly likely that it worked in the process of disease inducer rather than byproduct, and by deriving a metabolite closely related to the disease through additional target metabolomics related to sugar metabolism, research will be needed in the future.…”

G2019S LRRK2 Mutation Enhances MPP+-Induced Inflammation of Human Induced Pluripotent Stem Cells-Differentiated Dopaminergic Neurons

“…The etiopathogenesis of PD remains unclear. Although the majority of PD cases are idiopathic, the effects of mutations associated with familial PD, such as SNCA , LRRK2 , PARK2 , PINK1 , and GBA remain the focus of current research ( Zhang et al, 2021 ). There are still several obstacles to study PD despite the availability of mouse models and in vitro assays.…”

Metabolomics in Preclinical Drug Safety Assessment: Current Status and Future Trends

“…For instance, a study applied metabolomics to investigate the responses of metabolite profiles in zebrafish exposed to acetochlor and butachlor, two substances that could disrupt the thyroid and sex steroid endocrine systems in zebrafish [7]. Metabolomics can give insights into toxicity pathways and mechanisms, e.g., metabolomics is an emerging approach used to identify and discover metabolic biomarkers, providing a series of metabolic signatures that elucidate the pathological changes in diseases, including Parkinson's disease [8]. This technology links various metabolic molecular mechanisms to neuronal activity alterations, protein changes or genetic mutations, and mitochondrial dysfunction.…”