Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing

Nature reviews. Neuroscience, Journal Year: 2018, Volume and Issue: 19(11), P. 701 - 710

Published: Oct. 10, 2018

Language: Английский

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Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration

Translational Neurodegeneration, Journal Year: 2022, Volume and Issue: 11(1)

Published: Jan. 25, 2022

Abstract Glutamate is the most commonly engaged neurotransmitter in mammalian central nervous system, acting to mediate excitatory neurotransmission. However, high levels of glutamatergic input elicit excitotoxicity, contributing neuronal cell death following acute brain injuries such as stroke and trauma. While excitotoxic has also been implicated some neurodegenerative disease models, role apoptotic remains controversial setting chronic neurodegeneration. Nevertheless, it clear that synaptic dysregulation contributes neurodegeneration, evidenced by protective effects partial N -methyl- D -aspartate receptor antagonists. Here, we review evidence for sublethal relation neurodegeneration associated with Parkinson’s disease, Alzheimer’s amyotrophic lateral sclerosis Huntington’s disease. In contrast classic emerging implicates mitochondrial calcium handling post-synaptic We discuss mechanisms regulate uptake release, impact LRRK2, PINK1, Parkin, beta-amyloid glucocerebrosidase on transporters, autophagic loss axodendritic shrinkage. Finally, strategies normalizing flux into out matrix, thereby preventing toxicity dendritic loss. underlie increased or decreased release vary different model systems, a common set normalize can prevent may be neuroprotective multiple contexts.

Language: Английский

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“Is dopamine involved in Alzheimer's disease?”

Frontiers in Aging Neuroscience, Journal Year: 2014, Volume and Issue: 6

Published: Sept. 25, 2014

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and dementia. Recent advances indicate that AD pathogenesis appears more complex than its mere neuropathology. Changes in synaptic plasticity, neuronal disarray cell death are pathways commonly recognized as pathogenic mechanisms of AD. It thought the altered metabolism certain membrane proteins may lead to production amyloid (Aβ) oligomers an highly toxic effect on neurotransmission pathways, such those mediated Acetylcholine. The interaction Aβ with these neurotansmitters systems would turn induce dysfunction, neurotransmitters signaling imbalance finally appearance neurological signs. In this perspective, it still debated how if also engage dopaminergic system experimental work revealed well be involved occurrence decline, often being predictive rapidly forms However clear idea role dopamine missing. Here we review recent evidences supporting notion dysfunction has symptoms

Language: Английский

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Gut Bacteria and Neurotransmitters

Microorganisms, Journal Year: 2022, Volume and Issue: 10(9), P. 1838 - 1838

Published: Sept. 14, 2022

Gut bacteria play an important role in the digestion of food, immune activation, and regulation entero-endocrine signaling pathways, but also communicate with central nervous system (CNS) through production specific metabolic compounds, e.g., bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin (5-HT) histamine. Afferent vagus nerve (VN) fibers that transport signals from gastro-intestinal tract (GIT) gut microbiota to brain are linked receptors esophagus, liver, pancreas. In response these stimuli, sends back entero-epithelial cells via efferent VN fibers. Fibers not direct contact wall or intestinal microbiota. Instead, reach 100 500 million neurons enteric (ENS) submucosa myenteric plexus wall. The modulation, development, renewal ENS controlled by microbiota, especially those ability produce metabolize hormones. Signals generated hypothalamus pituitary adrenal glands hypothalamic axis (HPA). SCFAs produced adhere free (FFARs) on surface epithelial (IECs) interact enter circulatory system. alter synthesis degradation neurotransmitters. This review focuses effect have neurotransmitters vice versa.

Language: Английский

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Bioactive effects of quercetin in the central nervous system: Focusing on the mechanisms of actions

Biomedicine & Pharmacotherapy, Journal Year: 2016, Volume and Issue: 84, P. 892 - 908

Published: Oct. 15, 2016

Language: Английский

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Neurodegenerative Diseases – Is Metabolic Deficiency the Root Cause?

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: March 31, 2020

Neurodegenerative diseases, including Alzheimer, Parkinson, Huntington, and amyotrophic lateral sclerosis, are a prominent class of neurological diseases currently without cure. They characterized by an inexorable loss specific type neurons. The selective vulnerability neuronal clusters (typically subcortical cluster) in the early stages, followed spread disease to higher cortical areas, is typical pattern progression. share range molecular cellular pathologies, protein aggregation, mitochondrial dysfunction, glutamate toxicity, calcium load, proteolytic stress, oxidative neuroinflammation, aging, which contribute death. Efforts treat these often limited fact that they tend address any one above pathological changes while ignoring others. Lack clarity regarding possible root cause underlies all pathologies poses significant challenge. In search integrative theory for neurodegenerative pathology, we hypothesize metabolic deficiency certain vulnerable common underlying thread links many dimensions disease. current review aims present outline such theory. We new perspective as disorders at molecular, cellular, systems levels. This helps understand mechanism facets may lead more promising disease-modifying therapeutic interventions. Here, briefly discuss also involvement glia vascular dysfunctions. Any failure satisfaction demand neurons triggers chain events precipitate various manifestations pathology.

Language: Английский

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Toxoplasma gondii‐induced neuronal alterations

Parasite Immunology, Journal Year: 2014, Volume and Issue: 37(3), P. 159 - 170

Published: Nov. 6, 2014

The zoonotic pathogen Toxoplasma gondii infects over 30% of the human population. intracellular parasite can persist lifelong in CNS within neurons modifying their function and structure, thus leading to specific behavioural changes host. In recent years, several vitro studies murine models have focused on elucidation these modifications. Furthermore, investigations population correlated seropositivity with neurological functions; however, complex underlying mechanisms subtle alteration are still not fully understood. parasites able induce direct modifications infected cells, for example by altering dopamine metabolism, functionally silencing as well hindering apoptosis. Moreover, indirect effects peripheral immune system alterations status CNS, observed during chronic infection, might also contribute neuronal connectivity synaptic plasticity. this review, we will provide an overview highlight advances, which describe morphology upon T. infection.

Language: Английский

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Neuropharmacological Effects of Quercetin: A Literature-Based Review

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: June 17, 2021

Quercetin (QUR) is a natural bioactive flavonoid that has been lately very studied for its beneficial properties in many pathologies. Its neuroprotective effects have demonstrated vitro studies, as well vivo animal experiments and human trials. QUR protects the organism against neurotoxic chemicals also can prevent evolution development of neuronal injury neurodegeneration. The present work aimed to summarize literature about effect using known database sources. Besides, this review focuses on assessment potential utilization complementary or alternative medicine preventing treating neurodegenerative diseases. An up-to-date search was conducted PubMed, Science Direct Google Scholar published dealing with injury, treatment Findings suggest possess neuropharmacological protective brain disorders such Alzheimer’s disease, Amyloid β peptide, Parkinson’s Huntington's multiple sclerosis, amyotrophic lateral sclerosis. In summary, emphasizes advantages being used prevention o different

Language: Английский

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Alzheimer's and Parkinson's disease therapies in the clinic

Bioengineering & Translational Medicine, Journal Year: 2022, Volume and Issue: 8(1)

Published: Aug. 3, 2022

Abstract Alzheimer's disease (AD) and Parkinson's (PD) are the most prevalent neurodegenerative diseases, affecting millions costing billions each year in United States alone. Despite tremendous progress developing therapeutics that manage symptoms of these two scientific community has yet to develop a treatment effectively slows down, inhibits, or cures neurodegeneration. To gain better understanding current therapeutic frontier for AD PD, we provide review on past present strategies major disorders clinical trial process. We briefly recap currently US Food Drug Administration‐approved therapies, then explore trends trials across variables therapy mechanism intervention, administration route, use delivery vehicle, outcome measures, phases over time “Drug” “Biologic” therapeutics. success rate analyze intersections approaches revealing shift away from therapies targeting neurotransmitter systems symptomatic relief, towards anti‐aggregation, anti‐inflammatory, anti‐oxidant, regeneration aim inhibit root causes progression. also highlight evolving distribution types investigated, slowly increasing still severe under‐utilization vehicles PD discuss novel preclinical treating PD. Overall, this aims succinct overview landscape understand field's strategy evolution approach present, inform how treat future.

Language: Английский

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Amino Acid Catabolism in Alzheimer’s Disease Brain: Friend or Foe?

Oxidative Medicine and Cellular Longevity, Journal Year: 2017, Volume and Issue: 2017(1)

Published: Jan. 1, 2017

There is a dire need to discover new targets for Alzheimer’s disease (AD) drug development. Decreased neuronal glucose metabolism that occurs in AD brain could play central role progression. Little known about the compensatory changes occur attempt maintain energy homeostasis. In this review using PubMed literature database, we summarize evidence amino acid oxidation can temporarily compensate decreased metabolism, but eventually altered and catabolite levels likely lead toxicities contributing Because acids are involved so many cellular metabolic signaling pathways, effects of far‐reaching. Possible pathological results from several important discussed. Urea cycle function may be induced endothelial cells patient brains, possibly remove excess ammonia produced increased catabolism. Studying perspective provides insights into pathogenesis discovery dietary metabolite supplements partially alterations enzymatic delay or alleviate some suffering caused by disease.

Language: Английский

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