Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections DOI Creative Commons
Maura Rojas-Pirela, Diego Andrade-Alviárez, Verónica Rojas

et al.

Open Biology, Journal Year: 2025, Volume and Issue: 15(2)

Published: Feb. 1, 2025

Glycolysis, present in most organisms, is evolutionarily one of the oldest metabolic pathways. It has great relevance at a physiological level because it responsible for generating ATP cell through conversion glucose into pyruvate and reducing nicotinamide adenine dinucleotide (NADH) (that may be fed electron chain mitochondria to produce additional by oxidative phosphorylation), as well producing intermediates that can serve substrates other processes. Glycolysis takes place 10 consecutive chemical reactions, each which catalysed specific enzyme. Although energy transduction metabolism main function this pathway, involvement virulence, growth, pathogen–host interactions, immunomodulation adaptation environmental conditions are functions attributed pathway. In humans, where glycolysis occurs mainly cytosol, mislocalization some glycolytic enzymes various subcellular locations, alterations their expression regulation, been associated with development progression diseases. review, we describe role pathogenesis diseases clinical interest. addition, potential these targets drug use diagnostic prognostic markers pathologies also discussed.

Language: Английский

The interplay among oxidative stress, brain insulin resistance and AMPK dysfunction contribute to neurodegeneration in type 2 diabetes and Alzheimer disease DOI
Eugenio Barone, Fabio Di Domenico, Marzia Perluigi

et al.

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 176, P. 16 - 33

Published: Sept. 14, 2021

Language: Английский

Citations

104
Hippocampal disruptions of synaptic and astrocyte metabolism are primary events of early amyloid pathology in the 5xFAD mouse model of Alzheimer’s disease DOI Creative Commons
Jens V. Andersen, Niels H. Skotte, Sofie K. Christensen

et al.

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(11)

Published: Oct. 16, 2021

Abstract Alzheimer’s disease (AD) is an unremitting neurodegenerative disorder characterized by cerebral amyloid-β (Aβ) accumulation and gradual decline in cognitive function. Changes brain energy metabolism arise the preclinical phase of AD, suggesting important metabolic component early AD pathology. Neurons astrocytes function close collaboration, which essential for recycling neurotransmitters synapse. However, this crucial interplay during stages development has not been sufficiently investigated. Here, we provide integrative analysis cellular Aβ cortex hippocampus 5xFAD mouse model AD. Our electrophysiological examination revealed increase spontaneous excitatory signaling hippocampus. This hyperactive neuronal phenotype coincided with decreased hippocampal tricarboxylic acid (TCA) cycle mapped stable 13 C isotope tracing. Particularly, reduced astrocyte TCA activity glutamine synthesis led to hampered GABA In contrast, mice displayed elevated capacity oxidative glucose metabolism, may suggest a compensation region. We found limited changes when explored proteome metabolome mice, supporting that functional disturbances between neurons are primary events addition, synaptic mitochondrial glycolytic was selectively impaired hippocampus, whereas non-synaptic maintained. These findings were supported ultrastructural analyses demonstrating disruptions morphology, particularly Collectively, our study reveals complex regional cell-specific adaptations amyloid pathology, be fundamental progressing dysfunctions

Language: Английский

Citations

67
Integrated multi-omics analysis of Alzheimer’s disease shows molecular signatures associated with disease progression and potential therapeutic targets DOI Creative Commons
Pradeep Kodam,

R. Sai Swaroop,

Sai Sanwid Pradhan

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: March 6, 2023

Alzheimer's disease (AD) is a progressive neurodegenerative characterized by the formation of amyloid plaques implicated in neuronal death. Genetics, age, and sex are risk factors attributed to AD. Though omics studies have helped identify pathways associated with AD, an integrated systems analysis available data could help understand mechanisms, potential biomarkers, therapeutic targets. Analysis transcriptomic sets from GEO database, proteomic metabolomic literature was performed deregulated commonality identified overlapping among sets. The included those neurotransmitter synapses, oxidative stress, inflammation, vitamins, complement, coagulation pathways. Cell type showed microglia, endothelial, myeloid, lymphoid cells affected. Microglia inflammation pruning synapses implications for memory cognition. protein-cofactor network B2, B6, pantothenate shows metabolic modulated these vitamins which overlap multi-omics analysis. Overall, molecular signature Treatment anti-oxidants, genetically susceptible individuals pre-symptomatic stage might better management disease.

Language: Английский

Citations

41
Metabolic defects shared by Alzheimer's disease and diabetes: A focus on mitochondria DOI Creative Commons
Cristina Carvalho, Paula I. Moreira

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 79, P. 102694 - 102694

Published: Feb. 24, 2023

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two global epidemics that share several metabolic defects, such as insulin resistance, impaired glucose metabolism, mitochondrial defects. Importantly, strong evidence demonstrates T2D significantly increases the risk of cognitive decline dementia, particularly AD. Here, we provide an overview defects characterize link both pathologies putting focus on mitochondria. The biomarker potential components therapeutic some drugs target modulate mitochondria also briefly discussed.

Language: Английский

Citations

29
Hiding in Plain Sight: Modern Thiamine Deficiency DOI Creative Commons
Chandler Marrs,

Derrick Lonsdale

Cells, Journal Year: 2021, Volume and Issue: 10(10), P. 2595 - 2595

Published: Sept. 29, 2021

Thiamine or vitamin B1 is an essential, water-soluble required for mitochondrial energetics—the production of adenosine triphosphate (ATP). It a critical and rate-limiting cofactor to multiple enzymes involved in this process, including those at the entry points junctures glucose, fatty acid, amino acid pathways. has very short half-life, limited storage capacity, susceptible degradation depletion by number products that epitomize modern life, environmental pharmaceutical chemicals. The RDA thiamine 1.1–1.2 mg adult females males, respectively. With average diet, even poor one, it not difficult meet daily requirement, yet, measurable deficiency been observed across patient populations with incidence rates ranging from 20% over 90% depending upon study. This suggests requirement may be insufficient demands living. Inasmuch as syndromes pose great risk chronic morbidity, if left untreated, mortality, more comprehensive understanding chemistry, relative energy production, living, disease, prove useful.

Language: Английский

Citations

50
The role of NURR1 in metabolic abnormalities of Parkinson’s disease DOI Creative Commons
Murad Al‐Nusaif, Yuting Yang, Song Li

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: June 27, 2022

A constant metabolism and energy supply are crucial to all organs, particularly the brain. Age-dependent neurodegenerative diseases, such as Parkinson's disease (PD), associated with alterations in cellular metabolism. These changes have been recognized a novel hot topic that may provide new insights help identify risk pre-symptomatic phase of disease, understand pathogenesis, track progression, determine critical endpoints. Nuclear receptor-related factor 1 (NURR1), an orphan member nuclear receptor superfamily transcription factors, is major pathogenesis PD, NURR1 expression can detrimental effect on In this review, we discuss recent evidence suggests vital role dopaminergic (DAergic) neuron development PD. The association between metabolic abnormalities its implications for PD therapy further highlighted.

Language: Английский

Citations

32
Neuroprotective Mechanisms of Puerarin in Central Nervous System Diseases: Update DOI Creative Commons
Chao-Chao Yu,

Yan-Jun Du,

Jin Li

et al.

Aging and Disease, Journal Year: 2022, Volume and Issue: 13(4), P. 1092 - 1092

Published: Jan. 1, 2022

Due to global population aging and modern lifestyle changes, the incidence of central nervous system (CNS) disorders, such as neurodegenerative diseases, neuropsychiatric cerebrovascular is increasing has become a major public health challenge. Current medications commonly used in clinic are far from satisfactory may cause serious side effects. Therefore, identification novel drugs for effective management CNS diseases very urgent. Puerarin, highly bioactive ingredient isolated Pueraria lobata, known possess broad spectrum pharmacological properties including anti-diabetic, anti-inflammatory, anti-antioxidant, neuroprotective, cardioprotective features. However, its clinical application limited due poor water solubility. Since puerarin demonstrated wide range neuroprotective functions various Alzheimer's disease, Parkinson's cerebral ischemia, depression, spinal cord injury, it been attracting increasingly intense attention worldwide. In this review, we intend extensively summarize research progress on mechanisms recent years discuss future directions disease treatment.

Language: Английский

Citations

31
Aberrant energy metabolism in Alzheimer’s disease DOI Creative Commons
Linjie Yu, Jiali Jin, Yun Xu

et al.

Journal of Translational Internal Medicine, Journal Year: 2022, Volume and Issue: 10(3), P. 197 - 206

Published: Sept. 1, 2022

To maintain energy supply to the brain, a direct source called adenosine triphosphate (ATP) is produced by oxidative phosphorylation and aerobic glycolysis of glucose in mitochondria cytoplasm. Brain metabolism reduced many neurodegenerative diseases, including Alzheimer's disease (AD), where it appears presymptomatically progressive region-specific manner. Following dysregulation AD, cellular repair/regenerative processes are activated conserve required for cell viability. Glucose plays an important role pathology AD closely associated with tricarboxylic acid cycle, type 2 diabetes mellitus, insulin resistance. The intake neurons from endothelial cells, astrocytes, microglia. Damage neurocentric also damages transport systems AD. Gut microbiota necessary modulate bidirectional communication between gastrointestinal tract brain. may influence process regulating immune system maintaining integrity intestinal barrier. Furthermore, some therapeutic strategies have shown promising effects treatment at different stages, use antidiabetic drugs, rescuing mitochondrial dysfunction, epigenetic dietary intervention. This review discusses underlying mechanisms alterations provides potential

Language: Английский

Citations

30
New cyclophilin D inhibitor rescues mitochondrial and cognitive function in Alzheimer’s disease DOI
Sourav Samanta, Firoz Akhter, Anuradha Roy

et al.

Brain, Journal Year: 2023, Volume and Issue: 147(5), P. 1710 - 1725

Published: Dec. 26, 2023

Mitochondrial dysfunction is an early pathological feature of Alzheimer disease and plays a crucial role in the development progression Alzheimer's disease. Strategies to rescue mitochondrial function cognition remain be explored. Cyclophilin D (CypD), peptidylprolyl isomerase F (PPIase), key component opening membrane permeability transition pore, leading cell death. Blocking pore by inhibiting CypD activity promising therapeutic approach for However, there currently no effective inhibitor disease, with previous candidates demonstrating high toxicity, poor ability cross blood-brain barrier, compromised biocompatibility low selectivity. Here, we report new class non-toxic biocompatible inhibitor, ebselen, using conventional PPIase assay screen library ∼2000 FDA-approved drugs crystallographic analysis CypD-ebselen crystal structure (PDB code: 8EJX). More importantly, assessed effects genetic pharmacological blockade on glycolytic bioenergetics disease-derived cybrid cells, ex vivo human sporadic model, synaptic function, inflammatory response learning memory mouse models. Inhibition ebselen protects against disease- amyloid-β-induced perturbation, cognitive dysfunction, together suppressing neuroinflammation brain models, which linked CypD-related formation. Thus, inhibitors have potential slow neurodegenerative diseases, including boosting improving function.

Language: Английский

Citations

21
Icariin ameliorates glycolytic dysfunction in Alzheimer's disease models by activating the Wnt/β‐catenin signaling pathway DOI
Ju Liu,

Ai‐Hong Wei,

Tingting Liu

et al.

FEBS Journal, Journal Year: 2024, Volume and Issue: 291(10), P. 2221 - 2241

Published: Feb. 23, 2024

It was reported that the Wnt/β-catenin pathway is involved in regulation of aerobic glycolysis and brain glycolytic dysfunction results development Alzheimer's disease (AD). Icariin (ICA), an active component extracted from Epimedii Folium, has been to produce neuroprotective effects multiple models AD, but its underlying mechanism remains be fully described. We aimed investigate protective ICA on animal cell AD confirm whether functions function ICA. The 3 × Tg-AD mice were treated with HT22 cells, Aβ

Language: Английский

Citations

8