Metabolomics in Parkinson’s Disease and Correlation with Disease State DOI Creative Commons
Elena A. Ostrakhovitch, Kenjiro Ono, Tritia R. Yamasaki

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 208 - 208

Published: March 18, 2025

Changes in the level of metabolites, small molecules that are intermediates produced by metabolism or catabolism, associated with developing diseases. Metabolite signatures body fluids such as plasma, cerebrospinal fluid, urine, and saliva Parkinson’s disease. Here, we discuss alteration metabolites TCA cycle, pentose phosphate pathway, kynurenic network, redox system. We also summarize efforts many research groups to differentiate between metabolite profiles characterize PD motor progression dyskinesia, gait balance, non-motor symptoms depression cognitive decline. Understanding how changes lead may allow for identification individuals at earliest stage disease development new therapeutic strategies.

Language: Английский

Ageing as a risk factor for neurodegenerative disease DOI
Yujun Hou, Xiuli Dan, Mansi Babbar

et al.

Nature Reviews Neurology, Journal Year: 2019, Volume and Issue: 15(10), P. 565 - 581

Published: Sept. 9, 2019

Language: Английский

Citations

2418
Plasma membrane integrity in health and disease: significance and therapeutic potential DOI Creative Commons
Catarina Dias, Jesper Nylandsted

Cell Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: Jan. 19, 2021

Maintenance of plasma membrane integrity is essential for normal cell viability and function. Thus, robust repair mechanisms have evolved to counteract the eminent threat a torn membrane. Different bio-physical parameters required efficient are now emerging from different research groups. However, less known about when these come into play. This review focuses on existence disruptions in both physiological pathological conditions, across multiple types, albeit degrees. Fundamentally, irrespective source disruption, aberrant calcium influx common stimulus that activates response. Inadequate responses can tip balance between physiology pathology, highlighting significance integrity. For example, an over-activated response promote cancer invasion, while inability efficiently drive neurodegeneration muscular dystrophies. The interdisciplinary view explored here emphasises widespread potential targeting therapeutic purposes.

Language: Английский

Citations

176
Lipid droplets in the nervous system DOI Creative Commons
Isha Ralhan, Chi‐Lun Chang, Jennifer Lippincott‐Schwartz

et al.

The Journal of Cell Biology, Journal Year: 2021, Volume and Issue: 220(7)

Published: June 21, 2021

Lipid droplets are dynamic intracellular lipid storage organelles that respond to the physiological state of cells. In addition controlling cell metabolism, they play a protective role for many cellular stressors, including oxidative stress. Despite prior descriptions appearing in brain as early century ago, only recently has cells found begun be understood. droplet functions have now been described nervous system context development, aging, and an increasing number neuropathologies. Here, we review basic mechanisms formation, turnover, function discuss how these enable different types under healthy pathological conditions.

Language: Английский

Citations

154
Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans DOI Creative Commons
María Eugenia Goya, Feng Xue, Cristina Sampedro-Torres-Quevedo

et al.

Cell Reports, Journal Year: 2020, Volume and Issue: 30(2), P. 367 - 380.e7

Published: Jan. 1, 2020

Recent discoveries have implicated the gut microbiome in progression and severity of Parkinson's disease; however, how bacteria affect such neurodegenerative disorders remains unclear. Here, we report that Bacillus subtilis probiotic strain PXN21 inhibits α-synuclein aggregation clears preformed aggregates an established Caenorhabditis elegans model synucleinopathy. This protection is seen young aging animals partly mediated by DAF-16. Multiple B. strains trigger protective effect via both spores vegetative cells, due to a biofilm formation worms release bacterial metabolites. We identify several host metabolic pathways differentially regulated response exposure, including sphingolipid metabolism. further demonstrate functional roles metabolism genes lagr-1, asm-3, sptl-3 anti-aggregation effect. Our findings provide basis for exploring disease-modifying potential as dietary supplement.

Language: Английский

Citations

153
Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease DOI Creative Commons
Eleanor Sinclair, Drupad K. Trivedi, Depanjan Sarkar

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: March 11, 2021

Parkinson's disease (PD) is a progressive neurodegenerative disorder, which characterised by degeneration of distinct neuronal populations, including dopaminergic neurons the substantia nigra. Here, we use metabolomics profiling approach to identify changes lipids in PD observed sebum, non-invasively available biofluid. We used liquid chromatography-mass spectrometry (LC-MS) analyse 274 samples from participants (80 drug naïve PD, 138 medicated and 56 well matched control subjects) detected metabolites that could predict phenotype. Pathway enrichment analysis shows alterations lipid metabolism related carnitine shuttle, sphingolipid metabolism, arachidonic acid fatty biosynthesis. This study sebum can be potential biomarkers for PD.

Language: Английский

Citations

152
Brain lipidomics: From functional landscape to clinical significance DOI Creative Commons
Jong Hyuk Yoon, Youngsuk Seo, Yeon Suk Jo

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(37)

Published: Sept. 16, 2022

Lipids are crucial components of cellular function owing to their role in membrane formation, intercellular signaling, energy storage, and homeostasis maintenance. In the brain, lipid dysregulations have been associated with etiology progression neurodegeneration other neurological pathologies. Hence, brain lipids emerging as important potential targets for early diagnosis prognosis diseases. This review aims highlight significance usefulness lipidomics diagnosing treating We explored alterations diseases, paying attention organ-specific characteristics functions lipids. As recent advances would impossible without analytical techniques, we provide up-to-date information on mass spectrometric approaches integrative analysis omic approaches. Last, present applications combined artificial intelligence techniques interdisciplinary collaborative research diseases clinical heterogeneities.

Language: Английский

Citations

148
Autophagy lysosomal pathway dysfunction in Parkinson's disease; evidence from human genetics DOI
Konstantin Senkevich, Ziv Gan‐Or

Parkinsonism & Related Disorders, Journal Year: 2019, Volume and Issue: 73, P. 60 - 71

Published: Nov. 17, 2019

Language: Английский

Citations

110
Emerging Therapeutic Strategies for Parkinson’s Disease and Future Prospects: A 2021 Update DOI Creative Commons
Noha Gouda, Ahmed Elkamhawy,

Jungsook Cho

et al.

Biomedicines, Journal Year: 2022, Volume and Issue: 10(2), P. 371 - 371

Published: Feb. 3, 2022

Parkinson’s disease (PD) is a neurodegenerative disorder pathologically distinguished by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Muscle rigidity, tremor, and bradykinesia are all clinical motor hallmarks PD. Several pathways have been implicated PD etiology, including mitochondrial dysfunction, impaired protein clearance, neuroinflammation, but how these factors interact remains incompletely understood. Although many breakthroughs therapy accomplished, there currently no cure for PD, only trials to alleviate related symptoms. To reduce or stop progression mobility impairment, disease-modifying approach that can directly target etiology rather than offering symptomatic alleviation major unmet need management In this review, we briefly introduce current treatments pathophysiology addition, address novel innovative therapeutic targets therapy, α-synuclein, autophagy, neurodegeneration, others. immunomodulatory approaches stem cell research with patients also discussed. Moreover, preclinical studies evaluating efficacy repurposed agents their pragmatic applications encouraging outcomes summarized. Finally, molecular biomarkers under active investigation presented as potentially valuable tools early diagnosis.

Language: Английский

Citations

59
Ceramide accumulation induces mitophagy and impairs β-oxidation in PINK1 deficiency DOI Creative Commons
Melissa Vos,

Marija Dulovic‐Mahlow,

Frida Mandik

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(43)

Published: Oct. 22, 2021

Significance Ceramide accumulates in Parkinson’s disease–related PINK1 deficiency to initiate ceramide-mediated mitophagy as an alternative pathway overcome defective PINK1-related and the concomitant increased requirements for mitochondrial clearance. Increased ceramide levels negatively correlate with β-oxidation thus decrease efficiency of electron transport chain, further increasing need Interfering this vicious cycle can constitute a novel therapeutic strategy suggested by our data showing that reduction or stimulation improve -mutant phenotypes.

Language: Английский

Citations

58
Lipid Metabolism Influence on Neurodegenerative Disease Progression: Is the Vehicle as Important as the Cargo? DOI Creative Commons
Raja Elizabeth Estes, Bernice Lin, Arnav Khera

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2021, Volume and Issue: 14

Published: Dec. 20, 2021

Many neurodegenerative diseases are characterized by abnormal protein aggregates, including the two most common Alzheimer's disease (AD) and Parkinson's (PD). In global search to prevent treat diseases, research has been focused on early stages of how these pathogenic aggregates initially formed. We argue, however, that an equally important aspect etiology is characteristic spread throughout nervous system, a key process in progression. Growing evidence suggests both alterations lipid metabolism dysregulation extracellular vesicles (EVs) accelerate aggregation progression neurodegeneration, neurons potentially surrounding glia. will review pathways intertwined AD PD. Understanding metabolism, EV biogenesis, uptake regulate could reveal novel therapeutic targets slow or halt

Language: Английский

Citations

58