China
Africa
Explore chapters and articles related to this topic
Propionic acidemia
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Abnormal ketogenesis is a major cause of morbidity and mortality in this disease. It could result from a variety of mechanisms. Propionic acid is an inhibitor of mitochondrial oxidation of succinic and 2-ketoglutaric acid, and propionyl CoA is an inhibitor of succinate: CoA ligase, and malate dehydrogenase [69]. Carnitine prevents this, consistent with its role in therapy. Carnitine is depleted in these patients, because it forms the propionylcarnitine ester, which is excreted in the urine. Analysis for propionylcarnitine has also been used for diagnosis, and has been effectively explored in prenatal diagnosis [70]. The accumulation of propionyl CoA, and its condensation with oxalacetate to form methylcitrate depletes oxalacetate and so acetyl CoA, deprived of substrate with which to condense to form citrate, condenses with itself to form acetoacetate. A variety of mitochondrial oxidative functions have been found to be inhibited by propionic CoA [71] here including pyruvate dehydrogenase, 2-ketoglutarate dehydrogenase and decrease in the amount and activities of the OXPHOS complexes I–IV.
Alzheimer’s disease: a scoping review of biomarker research and development for effective disease diagnosis
Published in Expert Review of Molecular Diagnostics, 2022
Khushboo Govind Faldu, Jigna Samir Shah
Another study identified biomarker candidates in brain cortex, CSF, and serum samples in 365 AD, MCI patients, and healthy controls by performing proteome analysis by multiplexed tandem-mass-tag method, extensive LC-fractionation and high-resolution tandem MS for ultra-deep coverage which was followed by validation by ELISA. A total of 10 proteomic datasets comprising 17,541 proteins were analyzed. A decrease in mitochondrial proteins was observed in CSF samples of AD individuals. Thirty-seven proteins were identified across brain cortex, CSF, and serum as potential signature AD proteins of which 59% were mitochondrial proteins that emphasize the role of mitochondrial dysfunction in AD. For early diagnosis of AD, a biomarker panel can be developed with the most promising protein candidates identified that include netrin-1, secreted modular calcium-binding protein-1 (SMOC1), and succinate-CoA ligase GDP-forming subunit beta, tau protein, glial fibrillary acidic protein, and peroxiredoxin-3 [221].
Mitochondrial dysfunction in Alzheimer’s disease - a proteomics perspective
Published in Expert Review of Proteomics, 2021
Morteza Abyadeh, Vivek Gupta, Nitin Chitranshi, Veer Gupta, Yunqi Wu, Danit Saks, Roshana Wander Wall, Matthew J. Fitzhenry, Devaraj Basavarajappa, Yuyi You, Ghasem H Salekdeh, Paul a Haynes, Stuart L Graham, Mehdi Mirzaei
Currently, AD is diagnosed mainly based on clinical symptoms; however, it is clear that AD begins silently decades before clinical symptoms arise [80–82]; therefore finding reliable biomarkers is of paramount importance for early AD detection. Since the mitochondrial proteome alterations are known to occur in the early stages of AD, it can be considered as a promising potential source of biomarkers for early AD diagnosis. In this regard, Dey and colleagues (2019), in order to find blood-based biomarkers for AD, used TMT multiplexed proteomics in AD and control matched individuals. Selected protein validation was achieved using the TOMAHAQ technique (Triggered by Offset, Multiplexed, Accurate mass, high resolution and Absolute Quantitation). They identified 4826 proteins, of which 30 were differentially expressed. Of these, 26 were decreased in abundance and 4 were increased. Notably, 12 out of 26 down-regulated proteins were mitochondrial specific proteins. Intriguingly, tau and APP proteins were also identified in the analysis, but no statistically significant difference in their expression between AD and healthy samples was observed. The altered mitochondrial proteins included phosphoenolpyruvate carboxykinase (PEPCK), mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) and mitochondrial Adenylate kinase 2, (AK2). These proteins have the potential to be used as peripheral candidate biomarkers for AD progression (Table 1) [83]. Most recently, a landmark study performed by Wang and colleagues (2020) determined proteome changes in the cortex and cerebrospinal fluid (CSF) of AD subjects, and investigated the CSF changes in an AD mouse model in parallel, using a TMT labeling quantitative proteomics approach. In this study, a total of 13,833 proteins from human cortex, 5941 proteins from CSF and 4826 proteins from serum were identified and quantified. The findings were analyzed in context with previously published datasets on cortex, CSF and blood, to generate a shortlist of the most promising candidate biomarkers for AD from 10 proteomic datasets that covered 17,541 proteins from 365 AD, MCI and matched controls. Eventually, 37 differentially expressed proteins were identified as common in CSF, serum and cortex. Remarkably, 22 out of these 37 differentially expressed proteins were mitochondrial proteins intricately related to energy metabolism, showing mitochondrial alteration as a consistent change across human brain cortex, CSF and serum in AD. Finally, by integrating all the proteomic datasets, six proteins were identified as the most promising AD biomarkers, including two mitochondrial proteins, namely mitochondrial thioredoxin-dependent peroxide reductase (PRDX3), and mitochondrial succinate-CoA ligase [GDP-forming] subunit beta (SUCLG2) [84]. In a related study, an in-depth analysis of the CSF proteome of AD patients revealed a strong correlation between superoxide dismutase expression levels [Cu-Zn] (SODC) and AD status, suggesting it as a potential AD biomarker [85].