Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations DOI Creative Commons
Huiyuan Zhu, Dexi Bi, Youhua Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Jan. 17, 2022

The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate regimen that mimics the metabolism of fasting state to induce production ketone bodies. KD has long been established as remarkably successful dietary approach for treatment intractable epilepsy increasingly garnered research attention rapidly in past decade, subject emerging evidence promising therapeutic potential various diseases, besides epilepsy, from obesity malignancies. In this review, we summarize experimental and/or clinical efficacy safety different discuss possible mechanisms action based on recent advances understanding influence at cellular molecular levels. We emphasize may function through multiple mechanisms, which remain be further elucidated. challenges future directions implementation spectrum diseases have discussed. suggest that, with encouraging effects increasing insights into action, randomized controlled trials should conducted elucidate foundation use KD.

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

2410
Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease DOI Open Access

Eric Tönnies,

Eugenia Trushina

Journal of Alzheimer s Disease, Journal Year: 2017, Volume and Issue: 57(4), P. 1105 - 1121

Published: Jan. 6, 2017

Alzheimer's disease (AD) is a devastating neurodegenerative disorder without cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding mechanism hinders development efficacious therapeutic approaches. The loss synapses in affected brain regions correlates best with cognitive impairment patients and has been considered as early that precedes neuronal loss. Oxidative stress recognized contributing factor aging progression multiple diseases including AD. Increased production reactive oxygen species (ROS) associated age- disease-dependent mitochondrial function, altered metal homeostasis, reduced antioxidant defense directly affect synaptic activity neurotransmission neurons leading to dysfunction. In addition, molecular targets by ROS include nuclear DNA, lipids, proteins, calcium dynamics cellular architecture, receptor trafficking endocytosis, energy homeostasis. Abnormal metabolism turn could accumulation amyloid-β (Aβ) hyperphosphorylated Tau protein, which independently exacerbate dysfunction production, thereby vicious cycle. While mounting evidence implicates etiology, clinical trials therapies have not produced consistent results. this review, we will discuss role oxidative AD, innovative strategies evolved based on better complexity mechanisms dual play health disease.

Language: Английский

Citations

1471
The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease DOI Creative Commons
Jelske N. van der Veen, John P. Kennelly,

Sereana Wan

et al.

Biochimica et Biophysica Acta (BBA) - Biomembranes, Journal Year: 2017, Volume and Issue: 1859(9), P. 1558 - 1572

Published: April 11, 2017

Language: Английский

Citations

1155
Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives DOI
Sara Mostafalou, Mohammad Abdollahi

Toxicology and Applied Pharmacology, Journal Year: 2013, Volume and Issue: 268(2), P. 157 - 177

Published: Feb. 9, 2013

Language: Английский

Citations

1078
Role of oxidative stress in Alzheimer's disease DOI Creative Commons
Wenjuan Huang, Xia Zhang, Weiwei Chen

et al.

Biomedical Reports, Journal Year: 2016, Volume and Issue: 4(5), P. 519 - 522

Published: March 15, 2016

Alzheimer's disease (AD) is the most common cause of disability in individuals aged >65 years worldwide. AD characterized by abnormal deposition amyloid β (Aβ) peptide, and intracellular accumulation neurofibrillary tangles hyperphosphorylated τ protein dementia. The neurotoxic oligomer Aβ which neuropathological diagnostic criterion disease, together with protein, are mediators neurodegeneration that among main causative factors. However, these phenomena mainly initiated enhanced oxidative stress, a process referring to an imbalance between antioxidants oxidants favour oxidants. This can occur as result increased free radicals or decrease antioxidant defense, being species contains one more unpaired electrons its outer shell. major source potent reduction molecular oxygen water, initially yields superoxide radical, produces hydrogen peroxide addition electron. highly reactive hydroxyl radicals, termed (ROS) react lipids, proteins, nucleic acids, other molecules may also alter their structures functions. Thus, tissues organs, particularly brain, vulnerable organ, affected ROS due composition. brain largely composed easily oxidizable lipids while featuring high consumption rate. current review examined role stress AD.

Language: Английский

Citations

856
Mitochondria as a therapeutic target for common pathologies DOI
Michael P. Murphy, Richard C. Hartley

Nature Reviews Drug Discovery, Journal Year: 2018, Volume and Issue: 17(12), P. 865 - 886

Published: Nov. 5, 2018

Language: Английский

Citations

662
Chronic Glutamate Toxicity in Neurodegenerative Diseases—What is the Evidence? DOI Creative Commons
Jan Lewerenz, Pamela Maher

Frontiers in Neuroscience, Journal Year: 2015, Volume and Issue: 9

Published: Dec. 16, 2015

Together with aspartate, glutamate is the major excitatory neurotransmitter in brain. Glutamate binds and activates both ligand-gated ion channels (ionotropic receptors) a class of G-protein coupled receptors (metabotropic receptors). Although intracellular concentration brain millimolar range, extracellular kept low micromolar range by action amino acid transporters that import aspartate into astrocytes neurons. Excess may lead to excitotoxicity vitro vivo acute insults like ischemic stroke via overactivation ionotropic receptors. In addition, chronic has been hypothesized play role numerous neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease Huntington's disease. Based on this hypothesis, good deal effort devoted develop test drugs either inhibit or decrease glutamate. review, we provide an overview different pathways are thought over-activation glutamatergic system toxicity neurodegeneration. summarize available experimental evidence for animal models diseases.

Language: Английский

Citations

645
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis DOI Creative Commons
A. Aditya Prasad, Vidhya Bharathi, Vishwanath Sivalingam

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2019, Volume and Issue: 12

Published: Feb. 14, 2019

TAR DNA binding protein 43 (TDP-43) is a versatile RNA/DNA involved in RNA-related metabolism. Hyper-phosphorylated and ubiquitinated TDP-43 deposits as inclusion bodies the brain spinal cord of patients with motor neuron diseases: amyotrophic lateral sclerosis (ALS) frontotemporal lobar degeneration (FTLD). While majority ALS cases (90-95%) are sporadic (sALS), among familial 5-10% involve inheritance mutations TARDBP gene remaining due to other genes such as: C9ORF72, SOD1, FUS, NEK1 etc. Strikingly however, (up 97%) also contain deposited neuronal inclusions, which suggests its pivotal role pathology. Thus, unravelling molecular mechanisms pathology, seems central therapeutics, hence, we comprehensively review current understanding TDP-43's pathology ALS. We discuss roles mutations, cytoplasmic mis-localization aberrant post-translational modifications Also, evaluate amyloid-like vitro aggregation, physiological versus pathological oligomerization vivo, liquid-liquid phase separation (LLPS), potential prion-like propagation propensity inclusions. Finally, describe various evolving TDP-43-induced toxicity impairment endocytosis mitotoxicity emerging strategies towards disaggregation therapeutics.

Language: Английский

Citations

632
Mitochondrial disease in superoxide dismutase 2 mutant mice DOI
Simon Melov, Pınar Coşkun, Manisha Patel

et al.

Proceedings of the National Academy of Sciences, Journal Year: 1999, Volume and Issue: 96(3), P. 846 - 851

Published: Feb. 2, 1999

Oxidative stress has been implicated in many diseases. The chief source of reactive oxygen species within the cell is mitochondrion. We have characterized a variety biochemical and metabolic effects inactivation mouse gene for mitochondrial superoxide dismutase (CD1- Sod2 tm1Cje ). mutant mice exhibit tissue-specific inhibition respiratory chain enzymes NADH-dehydrogenase (complex I) succinate dehydrogenase II), tricarboxylic acid cycle enzyme aconitase, development urine organic aciduria conjunction with partial defect 3-hydroxy-3-methylglutaryl-CoA lyase, accumulation oxidative DNA damage. These results indicate that increase can result aberrations features reminiscent myopathy, Friedreich ataxia, lyase deficiency.

Language: Английский

Citations

583
Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells DOI Open Access

Hindupur K. Anandatheerthavarada,

Gopa Biswas,

Marie‐Anne Robin

et al.

The Journal of Cell Biology, Journal Year: 2003, Volume and Issue: 161(1), P. 41 - 54

Published: April 14, 2003

Alzheimer's amyloid precursor protein 695 (APP) is a plasma membrane protein, which known to be the source of toxic beta (Abeta) peptide associated with pathogenesis disease (AD). Here we demonstrate that by virtue its chimeric NH2-terminal signal, APP also targeted mitochondria cortical neuronal cells and select regions brain transgenic mouse model for AD. The positively charged residues at 40, 44, 51 are critical components mitochondrial-targeting signal. Chemical cross-linking together immunoelectron microscopy show mitochondrial exists in inside transmembrane orientation contact translocase proteins. Mutational studies acidic domain, spans sequence 220-290 APP, causes arrest COOH-terminal 73-kD portion facing cytoplasmic side. Accumulation full-length compartment transmembrane-arrested form, but not lacking caused dysfunction impaired energy metabolism. These results show, first time, under some physiological pathological conditions.

Language: Английский

Citations

552