Increased oxidation of certain glycolysis and energy metabolism enzymes in the frontal cortex in Lewy body diseases

2009 ◽  
Vol 87 (4) ◽  
pp. 1002-1013 ◽  
Author(s):  
Anna Gómez ◽  
Isidre Ferrer
Keyword(s):  
Energy Metabolism ◽  
Frontal Cortex ◽  
Lewy Body ◽  
Metabolism Enzymes ◽  
Lewy Body Diseases

scholarly journals Transcriptional network analysis in frontal cortex in Lewy body diseases with focus on dementia with Lewy bodies

2017 ◽  
Vol 28 (3) ◽  
pp. 315-333 ◽  
Author(s):  
Gabriel Santpere ◽  
Paula Garcia-Esparcia ◽  
Pol Andres-Benito ◽  
Belen Lorente-Galdos ◽  
Arcadi Navarro ◽  
...  
Keyword(s):  
Network Analysis ◽  
Frontal Cortex ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Transcriptional Network ◽  
Lewy Body Diseases

scholarly journals Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy body diseases

2021 ◽  
Author(s):  
Rahel Feleke ◽  
Regina H. Reynolds ◽  
Amy M. Smith ◽  
Bension Tilley ◽  
Sarah A. Gagliano Taliun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Lewy Body ◽  
Molecular Mechanisms ◽  
Lewy Bodies ◽  
Subsequent Development ◽  
Lewy Body Dementia ◽  
Anterior Cingulate ◽  
Lewy Body Diseases

AbstractParkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms underlying PDD and DLB remain largely unknown, a knowledge gap that presents an impediment to the discovery of disease-modifying therapies. Transcriptomic profiling can contribute to addressing this gap, but remains limited in the LBDs. Here, we applied paired bulk-tissue and single-nucleus RNA-sequencing to anterior cingulate cortex samples derived from 28 individuals, including healthy controls, PD, PDD and DLB cases (n = 7 per group), to transcriptomically profile the LBDs. Using this approach, we (i) found transcriptional alterations in multiple cell types across the LBDs; (ii) discovered evidence for widespread dysregulation of RNA splicing, particularly in PDD and DLB; (iii) identified potential splicing factors, with links to other dementia-related neurodegenerative diseases, coordinating this dysregulation; and (iv) identified transcriptomic commonalities and distinctions between the LBDs that inform understanding of the relationships between these three clinical disorders. Together, these findings have important implications for the design of RNA-targeted therapies for these diseases and highlight a potential molecular “window” of therapeutic opportunity between the initial onset of PD and subsequent development of Lewy body dementia.

scholarly journals The spectrum of cognitive impairment in Lewy body diseases

2014 ◽  
Vol 29 (5) ◽  
pp. 608-621 ◽  
Author(s):  
Jennifer G. Goldman ◽  
Caroline Williams-Gray ◽  
Roger A. Barker ◽  
John E. Duda ◽  
James E. Galvin
Keyword(s):  
Cognitive Impairment ◽  
Lewy Body ◽  
Lewy Body Diseases

scholarly journals Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability?

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Yoshiki Takamatsu ◽  
Masayo Fujita ◽  
Gilbert J. Ho ◽  
Ryoko Wada ◽  
Shuei Sugama ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Body ◽  
Gastrointestinal Symptoms ◽  
Lewy Bodies ◽  
Antagonistic Pleiotropy ◽  
Nonmotor Symptoms ◽  
Novel Therapy ◽  
Wide Range ◽  
Lewy Body Diseases

Lewy body diseases, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are associated with a wide range of nonmotor symptoms (NMS), including cognitive impairment, depression and anxiety, sleep disorders, gastrointestinal symptoms, and autonomic failure. The reason why such diverse and disabling NMS have not been weeded out but have persisted across evolution is unknown. As such, one possibility would be that the NMS might be somehow beneficial during development and/or reproductive stages, a possibility consistent with our recent view as to the evolvability of amyloidogenic proteins (APs) such as α-synuclein (αS) and amyloid-β (Aβ) in the brain. Based on the heterogeneity of protofibrillar AP forms in terms of structure and cytotoxicity, we recently proposed that APs might act as vehicles to deliver information regarding diverse internal and environmental stressors. Also, we defined evolvability to be an epigenetic phenomenon whereby APs are transgenerationally transmitted from parents to offspring to cope with future brain stressors in the offspring, likely benefitting the offspring. In this context, the main objective is to discuss whether NMS might be relevant to evolvability. According to this view, information regarding NMS may be transgenerationally transmitted by heterogeneous APs to offspring, preventing or attenuating the stresses related to such symptoms. On the other hand, NMS associated with Lewy body pathology might manifest through an aging-associated antagonistic pleiotropy mechanism. Given that NMS are not only specific to Lewy body diseases but also displayed in other disorders, including amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), these conditions might share common mechanisms related to evolvability. This might give insight into novel therapy strategies based on antagonistic pleiotropy rather than on individual NMS from which to develop disease-modifying therapies.

Intralaminar nuclei of the thalamus in Lewy body diseases

2009 ◽  
Vol 78 (2-3) ◽  
pp. 97-104 ◽  
Author(s):  
Daniel Brooks ◽  
Glenda M. Halliday
Keyword(s):  
Lewy Body ◽  
Intralaminar Nuclei ◽  
Lewy Body Diseases

scholarly journals Hepatic Cystathionine β-Synthase Activity is Increased by Greater Post-ruminal Supply of Methionine During the Periparturient Period in Dairy Cows

2019 ◽  
Author(s):  
Mario Vailati-Riboni ◽  
Fernanda Batistel ◽  
Rainie R C S Yambao ◽  
Claudia Parys ◽  
Yuan-Xiang Pan ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Dairy Cows ◽  
Carbon Metabolism ◽  
Production Efficiency ◽  
Fumarate Hydratase ◽  
Mrna Abundance ◽  
Periparturient Period ◽  
Inflammatory Status ◽  
Metabolism Enzymes ◽  
One Carbon Metabolism

Abstract Background Post-ruminal supply of Met during the periparturient period enhances production efficiency (feed conversion to milk) in dairy cows partly through alleviation of oxidant and inflammatory status. Whether alterations in hepatic one-carbon (major contributor of antioxidants) and/or energy-metabolism contribute to these beneficial effects is unknown. Objectives Investigate alterations in hepatic one-carbon and energy metabolism and associations with plasma amino acids (AA) and production efficiency in response to enhanced post-ruminal supply of Met. Methods Holstein cows (n = 30/group) were fed during the last 28 days of pregnancy a control diet (CON) or the control plus ethyl-cellulose rumen-protected methionine (MET; 0.9 g·kg−1 of dry matter intake). Plasma (n = 15/group) and liver tissue (n = 10/group) were collected throughout the periparturient period to evaluate AA profiles, activity of TCA cycle, and one-carbon metabolism via mRNA abundance, enzyme activity, and targeted metabolomics. Results Cows in MET had greater overall (27%, P = 0.027) plasma Met concentrations, but had similar total plasma AA concentrations. Although mRNA abundance of one-carbon metabolism enzymes did not differ, hepatic activity of cystathionine β-synthase (CBS) (51.2 vs. 44.4 mmol·h−1·mg−1 protein; P = 0.032) and concentration (19%, P = 0.048) of the cellular antioxidant glutathione were greater overall in MET. mRNA abundance of aconitase 2 and fumarate hydratase was greater overall (P = 0.049), and phosphoenolpyruvate carboxykinase 1 tended (P = 0.093) to be greater overall in cows fed MET. There was a tendency (P ≤ 0.093) for greater overall hepatic concentrations of malic acid, α-ketoglutaric acid, and isocitric acid in cows fed MET. Conclusions Greater activity of CBS in response to enhanced post-ruminal supply of Met likely contributes to alleviating oxidant status by increasing concentrations of glutathione. Hence, transsulfuration plays an important role in the observed improvements in production efficiency of dairy cows during the periparturient period.

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