Autophagy and apoptosis dysfunction in neurodegenerative disorders

Progress in Neurobiology, Journal Year: 2013, Volume and Issue: 112, P. 24 - 49

Published: Nov. 6, 2013

Autophagy and apoptosis are basic physiologic processes contributing to the maintenance of cellular homeostasis. encompasses pathways that target long-lived cytosolic proteins damaged organelles. It involves a sequential set events including double membrane formation, elongation, vesicle maturation finally delivery targeted materials lysosome. Apoptotic cell death is best described through its morphology. characterized by rounding, blebbing, cytoskeletal collapse, cytoplasmic condensation, fragmentation, nuclear pyknosis, chromatin condensation/fragmentation, formation membrane-enveloped apoptotic bodies, rapidly phagocytosed macrophages or neighboring cells. Neurodegenerative disorders becoming increasingly prevalent, especially in Western societies, with larger percentage members living an older age. They have be seen not only as health problem, but since they care-intensive, also carry significant economic burden. Deregulation autophagy plays pivotal role etiology and/or progress many these diseases. Herein, we briefly review latest findings indicate involvement neurodegenerative We provide brief introduction focusing on mitochondria lysosomes. then highlight pathophysiology common like Alzheimer's diseases, Parkinson's disease, Huntington's disease Amyotrophic lateral sclerosis. Then, describe functions brain homeostasis, context aforementioned disorders. Finally, discuss different ways modulation may employed for therapeutic intervention during

Language: Английский

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Clinical Practice Guideline: Tinnitus

Otolaryngology, Journal Year: 2014, Volume and Issue: 151(S2)

Published: Oct. 1, 2014

Objective Tinnitus is the perception of sound without an external source. More than 50 million people in United States have reported experiencing tinnitus, resulting estimated prevalence 10% to 15% adults. Despite high tinnitus and its potential significant effect on quality life, there are no evidence‐based, multidisciplinary clinical practice guidelines assist clinicians with management. The focus this guideline that both bothersome persistent (lasting 6 months or longer), which often negatively affects patient's life. target audience for any clinician, including nonphysicians, involved managing patients tinnitus. patient population limited adults (18 years older) primary bothersome. Purpose purpose provide evidence‐based recommendations This provides a logical framework improve care mitigate personal social effects persistent, It will discuss evaluation selection timing diagnostic testing specialty referral identify underlying treatable pathology. then treatment guide measurement determine most appropriate interventions symptoms life sufferers. Action Statements development group made strong recommendation distinguish from nonbothersome against obtaining imaging studies head neck specifically evaluate does not localize 1 ear, nonpulsatile, associated focal neurologic abnormalities asymmetric hearing loss. panel following : Clinicians should (a) perform targeted history physical examination at initial presumed conditions if promptly identified managed may relieve tinnitus; (b) obtain prompt, comprehensive audiologic unilateral, (≥ months), difficulties; (c) recent onset those months) prioritize intervention facilitate discussions about natural follow‐up care; (d) educate management strategies; (e) recommend aid who documented loss; (f) cognitive behavioral therapy recommended antidepressants, anticonvulsants, anxiolytics, intratympanic medications routine Ginkgo biloba, melatonin, zinc, other dietary supplements treating transcranial magnetic stimulation provided options present (regardless laterality, duration, perceived status); regarding acupuncture

Language: Английский

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Melatonin and inflammation—Story of a double‐edged blade

Journal of Pineal Research, Journal Year: 2018, Volume and Issue: 65(4)

Published: Sept. 22, 2018

Melatonin is an immune modulator that displays both pro- and anti-inflammatory properties. Proinflammatory actions, which are well documented by many studies in isolated cells or leukocyte-derived cell lines, can be assumed to enhance the resistance against pathogens. However, they detrimental autoimmune diseases. Anti-inflammatory actions of particular medicinal interest, because observed high-grade inflammation such as sepsis, ischemia/reperfusion, brain injury, also low-grade during aging neurodegenerative The mechanisms contributing effects manifold comprise various pathways secondary signaling. These include numerous antioxidant effects, downregulation inducible inhibition neuronal NO synthases, cyclooxygenase-2, high-mobility group box-1 signaling toll-like receptor-4 activation, prevention inflammasome NLRP3 NF-κB activation upregulation nuclear factor erythroid 2-related 2 (Nrf2). reflected proinflammatory cytokines. amyloid-β peptides reduced enhancing α-secretase β- γ-secretases. A role melatonin's seems associated with sirtuin-1 (SIRT1), shares known from melatonin additionally interferes mechanistic target rapamycin (mTOR) Notch, reduces expression lncRNA-CCL2. conclusion on a partial mediation SIRT1 supported repeatedly inhibitions sirtuin inhibitors knockdown.

Language: Английский

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Dietary Sources and Bioactivities of Melatonin

Nutrients, Journal Year: 2017, Volume and Issue: 9(4), P. 367 - 367

Published: April 7, 2017

Insomnia is a serious worldwide health threat, affecting nearly one third of the general population. Melatonin has been reported to improve sleep efficiency and it was found that eating melatonin-rich foods could assist sleep. During last decades, melatonin widely identified qualified in various from fungi animals plants. Eggs fish are higher melatonin-containing food groups animal foods, whereas plant nuts with highest content melatonin. Some kinds mushrooms, cereals germinated legumes or seeds also good dietary sources It proved concentration human serum significantly increase after consumption containing food. Furthermore, studies show exhibits many bioactivities, such as antioxidant activity, anti-inflammatory characteristics, boosting immunity, anticancer cardiovascular protection, anti-diabetic, anti-obese, neuroprotective anti-aging activity. This review summaries bioactivities melatonin, special attention paid mechanisms action.

Language: Английский

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An update on the rotenone models of Parkinson's disease: Their ability to reproduce the features of clinical disease and model gene–environment interactions

NeuroToxicology, Journal Year: 2014, Volume and Issue: 46, P. 101 - 116

Published: Dec. 13, 2014

Language: Английский

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Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases

Entropy, Journal Year: 2013, Volume and Issue: 15(4), P. 1416 - 1463

Published: April 18, 2013

Glyphosate, the active ingredient in Roundup®, is most popular herbicide used worldwide. The industry asserts it minimally toxic to humans, but here we argue otherwise. Residues are found main foods of Western diet, comprised primarily sugar, corn, soy and wheat. Glyphosate's inhibition cytochrome P450 (CYP) enzymes an overlooked component its toxicity mammals. CYP play crucial roles biology, one which detoxify xenobiotics. Thus, glyphosate enhances damaging effects other food borne chemical residues environmental toxins. Negative impact on body insidious manifests slowly over time as inflammation damages cellular systems throughout body. Here, show how interference with acts synergistically disruption biosynthesis aromatic amino acids by gut bacteria, well impairment serum sulfate transport. Consequences diseases conditions associated a include gastrointestinal disorders, obesity, diabetes, heart disease, depression, autism, infertility, cancer Alzheimer’s disease. We explain documented ability induce that “textbook example” exogenous semiotic entropy: homeostasis

Language: Английский

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Clarifying the role of sleep in depression: A narrative review

Psychiatry Research, Journal Year: 2020, Volume and Issue: 291, P. 113239 - 113239

Published: June 16, 2020

Language: Английский

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Long‐term melatonin treatment delays ovarian aging

Journal of Pineal Research, Journal Year: 2016, Volume and Issue: 62(2)

Published: Nov. 27, 2016

Ovarian aging is characterized by gradual declines in oocyte quantity and quality. Melatonin considered an anti-aging agent due to its cytoprotective actions as antioxidant. This study examined whether long-term melatonin treatment would delay ovarian mice. Female ICR mice (10 weeks old) were given melatonin-containing water (100 μg/mL; melatonin) or only until 43 of age. Their oocytes recovered from the oviduct, vitro fertilization was performed. The ovaries used for a histological analysis number follicles. mRNA expression aging-related sirtuin genes (SIRT1, SIRT3) autophagy-related gene (LC3) telomere length chromosomes analyzed. Transcriptome changes also using microarray. ovulated decreased with age; however, it greater melatonin-treated than that control animals. rate blastocyst during higher controls, numbers primordial, primary, antral SIRT1 LC3 enhanced treatment. Seventy-eight downregulated upregulated identified microarray analysis. Forty these 78 ribosome-related genes, free radical scavenging network identified. present results indicate delays multiple mechanisms including antioxidant action, maintaining telomeres, stimulating SIRT ribosome function, reducing autophagy.

Language: Английский

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New horizons for newborn brain protection: enhancing endogenous neuroprotection

Archives of Disease in Childhood Fetal & Neonatal, Journal Year: 2015, Volume and Issue: 100(6), P. F541 - F552

Published: June 10, 2015

Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution pure hypoxia-ischaemia (HI) NE has been debated; over last decade, sensitising effect inflammation aetiology neurodisability is recognised. Therapeutic hypothermia standard care for high-income countries; however, its benefit encephalopathic babies sepsis or those born following chorioamnionitis unclear. It now recognised that phases brain injury extend into tertiary phase, which lasts weeks years after initial opens up new possibilities therapy.There recent focus on understanding endogenous neuroprotection how boost it supplement effectors therapeutically once damage occurred as NE. In this review, we strategies can augment body's own neuroprotection. We discuss particular remote ischaemic postconditioning whereby tolerance be activated through hypoxia/reperfusion stimuli started immediately index hypoxic-ischaemic insult. hypothermia, melatonin, erythropoietin cannabinoids examples ways response HI obtain full neuroprotective potential. Achieving correct balance interventions at time relation nature stage will significant challenge next decade.

Language: Английский

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Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer's disease

Acta Biochimica et Biophysica Sinica, Journal Year: 2017, Volume and Issue: 49(10), P. 853 - 866

Published: June 23, 2017

Alzheimer's disease (AD) is a neurodegenerative disease, in which the primary etiology remains unknown. AD presents amyloid beta (Aβ) protein aggregation and neurofibrillary plaque deposits. shows oxidative stress chronic inflammation. In AD, canonical Wingless-Int (Wnt)/β-catenin pathway downregulated, whereas peroxisome proliferator-activated receptor γ (PPARγ) increased. Downregulation of Wnt/β-catenin, through activation glycogen synthase kinase-3β (GSK-3β) by Aβ, inactivation phosphatidylinositol 3-kinase/Akt signaling involve AD. Cannabidiol (CBD) non-psychotomimetic phytocannabinoid from Cannabis sativa plant. PC12 cells, Aβ-induced tau hyperphosphorylation inhibited CBD. This inhibition associated with downregulation p-GSK-3β, an inhibitor Wnt pathway. CBD may also increase Wnt/β-catenin stimulation PPARγ, Aβ ubiquitination precursor protein. attenuates diminishes mitochondrial dysfunction reactive oxygen species generation. suppresses, pro-inflammatory be potential new candidate for therapy.

Language: Английский

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