Astrocyte dysfunction in Alzheimer disease

Journal of Neuroscience Research, Journal Year: 2017, Volume and Issue: 95(12), P. 2430 - 2447

Published: May 3, 2017

Abstract Astrocytes are glial cells that distributed throughout the central nervous system in an arrangement optimal for chemical and physical interaction with neuronal synapses brain blood supply vessels. Neurotransmission modulates astrocytic excitability by activating array of cell surface receptors transporter proteins, resulting dynamic changes intracellular Ca 2+ or Na + . Ionic electrogenic changes, turn, drive vital nonautonomous effects supporting function, including regulation synaptic activity, metabolism, regional supply. Alzheimer disease (AD) is associated aberrant oligomeric amyloid β generation, which leads to extensive proliferation astrocytes a reactive phenotype abnormal these processes. Astrocytic morphology, responses, extracellular K removal, glutamate transport, clearance, energy metabolism all affected AD, deleterious set includes excitotoxicity, impaired plasticity, reduced carbon delivery neurons oxidative phosphorylation, dysregulated linkages between demand This review summarizes how AD describes likely influence function. © 2017 Wiley Periodicals, Inc.

Language: Английский

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Mechanisms of Alzheimer’s Disease Pathogenesis and Prevention: The Brain, Neural Pathology, N-methyl-D-aspartate Receptors, Tau Protein and Other Risk Factors

Clinical Psychopharmacology and Neuroscience, Journal Year: 2017, Volume and Issue: 15(1), P. 1 - 8

Published: Jan. 25, 2017

Other SectionsAbstractINTRODUCTIONBRAIN AND ANATOMYNEURAL MECHANISMSPATHOGENESIS OF ALZHEIMER’S DISEASEALZHEIMER’S DISEASE NMDA RECEPTORSTAU PROTEINBRAIN-DERIVED NEUROTROPHIC FACTOR DISEASEANIMAL MODELS BEHAVIORRISK FACTORSCOGNITIVE RESERVE PREVENTIONCONCLUSIONSFiguresReferences

Language: Английский

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Therapeutic strategies and nano-drug delivery applications in management of ageing Alzheimer’s disease

Drug Delivery, Journal Year: 2018, Volume and Issue: 25(1), P. 307 - 320

Published: Jan. 1, 2018

In recent years, the incidental rate of neurodegenerative disorders has increased proportionately with aging population. Alzheimer's disease (AD) is one most commonly reported disorders, and it estimated to increase by roughly 30% among aged spite screening numerous drug candidates against various molecular targets AD, only a few – such as acetylcholinesterase inhibitors are currently utilized an effective clinical therapy. However, targeted delivery these drugs central nervous system (CNS) exhibits several limitations including meager solubility, low bioavailability, reduced efficiency due impediments blood-brain barrier (BBB). Current advances in nanotechnology present opportunities overcome delivering active candidates. Nanodrug systems promising targeting therapeutic moieties easing penetration molecules across CNS improving their bioavailability. Recently, wide range nano-carriers, polymers, emulsions, lipo-carriers, solid lipid carriers, carbon nanotubes, metal based carriers etc., have been adapted develop successful therapeutics sustained release improved efficacy. Here, we discuss recently updated nano-drug applications that field AD therapeutics, future prospects on potential for systems.

Language: Английский

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Dietary regulation of PI3K/AKT/GSK-3β pathway in Alzheimer’s disease

Alzheimer s Research & Therapy, Journal Year: 2014, Volume and Issue: 6(3)

Published: June 20, 2014

Abstract Alzheimer’s disease (AD) is characterized by the formation of senile plaques and neurofibrillary tangles composed phosphorylated Tau. Several findings suggest that correcting signal dysregulation for Tau phosphorylation in AD may offer a potential therapeutic approach. The PI3K/ AKT /GSK-3β pathway has been shown to play pivotal role neuroprotection, enhancing cell survival stimulating proliferation inhibiting apoptosis. This appears be crucial because it promotes protein hyper-phosphorylation Understanding those regulations provide better efficacy new approaches. In this review, we summarize advances involvement pathways signaling neuronal cells. We also review recent studies on features several diets involved AD.

Language: Английский

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Astrocyte senescence promotes glutamate toxicity in cortical neurons

PLoS ONE, Journal Year: 2020, Volume and Issue: 15(1), P. e0227887 - e0227887

Published: Jan. 16, 2020

Neurodegeneration is a major age-related pathology. Cognitive decline characteristic of patients with Alzheimer's and related dementias cancer after chemo- or radio-therapies. A recently emerged driver these other pathologies cellular senescence, cell fate that entails permanent cycle arrest pro-inflammatory senescence-associated secretory phenotype (SASP). Although there link between inflammation neurodegenerative diseases, are many open questions regarding how senescence affects pathologies. Among the various types in brain, astrocytes most abundant. Astrocytes have proliferative capacity essential for neuron survival. Here, we investigated primary human made senescent by X-irradiation, identified genes encoding glutamate potassium transporters as specifically downregulated upon senescence. This down regulation led to neuronal death co-culture assays. Unbiased RNA sequencing transcripts expressed non-senescent confirmed homeostasis pathway declines Our results suggest key role particularly astrocytes, excitotoxicity, which may lead neurodegeneration including disease dementias.

Language: Английский

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Nanomaterial based drug delivery systems for the treatment of neurodegenerative diseases

Biomaterials Science, Journal Year: 2020, Volume and Issue: 8(15), P. 4109 - 4128

Published: Jan. 1, 2020

With an aging population that has been increasing in recent years, the need for development of therapeutic approaches treatment neurodegenerative disorders (ND) increased. ND, which are characterized by progressive loss structure or function neurons, often associated with neuronal death. In spite screening numerous drugs, currently there is no specific can cure these diseases slow down their progression. Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Huntington's disease, and prion belong to ND affect enormous numbers people globally. There some main possible reasons failure such as limitations introduced Blood-Brain Barrier (BBB), Blood-Cerebrospinal Fluid (BCFB) P-glycoproteins. Current advances nanotechnology present opportunities overcome mentioned using designing nanomaterials improving delivery active drug candidates. Some basic developing strategies impediments local receptor-mediated transcytosis, physicochemical disruption BBB, cell-penetrating peptides magnetic disruption. Recently, application nanoparticles developed improve efficiency delivery. Nanoengineered particles nanodrugs possess capacity cross BBB also show decreased invasiveness. Examples include inorganic, magnetic, polymeric carbonic have efficiency. Despite papers published this filed, unsolved issues be addressed successful diseases. These discussed herein.

Language: Английский

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The Biology and Pathobiology of Glutamatergic, Cholinergic, and Dopaminergic Signaling in the Aging Brain

Frontiers in Aging Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: July 13, 2021

The elderly population is growing worldwide, with important health and socioeconomic implications. Clinical experimental studies on aging have uncovered numerous changes in the brain, such as decreased neurogenesis, increased synaptic defects, greater metabolic stress, enhanced inflammation. These are associated cognitive decline neurobehavioral deficits. Although not a disease, it significant risk factor for functional worsening, affective impairment, disease exaggeration, dementia, general susceptibility. Conversely, life events related to mental stress trauma can also lead accelerated age-associated disorders dementia. Here, we review human mice rats, those modeling neurodegenerative diseases, that helped elucidate (1) dynamics mechanisms underlying biological pathological of main projecting systems brain (glutamatergic, cholinergic, dopaminergic) (2) effect defective glutamatergic, dopaminergic projection disabilities disorders, Alzheimer’s Parkinson’s diseases. Detailed knowledge age-related diseases be an element development effective ways treatment. In this context, briefly analyze which adverse glutaminergic could targeted by therapeutic strategies developed result our better understanding these damaging mechanisms.

Language: Английский

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Amyloid β, Glutamate, Excitotoxicity in Alzheimer's Disease: Are We on the Right Track?

CNS Neuroscience & Therapeutics, Journal Year: 2013, Volume and Issue: 19(8), P. 549 - 555

Published: April 18, 2013

Alzheimer's disease (AD) has a devastating impact on aged people worldwide. Although sophisticated and advanced molecular methods have been developed for its diagnosis since early phases, pharmacological treatment still represents an unresolved topic. The more the progresses, uneffectiveness of antidementia drugs emerges. New encouraging results from experimental works indicate that glutamate pathway may play substantial role in pathogenesis stages disease. Several data together with clinical use uncompetitive N-methyl-d-aspartate (NMDA) antagonist memantine strengthen this idea. Unfortunately, definitive glutamatergic transmission involvement AD are incomplete. Moreover, only temporarily limited effects memantine. Currently, is indicated moderate-to-severe cases AD, indication limit efficacy dementia. association acetylcholinesterase inhibitor used to treat dementia symptoms appears be beneficial, both studies. Because cholinergic dysfunction occurs coadministration appropriate might represent valid option beginning cognitive decline. better evaluate drug efficacy, recently introduced biomarkers profile should considered aim pursue.

Language: Английский

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Aberrant iPSC-derived human astrocytes in Alzheimer's disease

Cell Death and Disease, Journal Year: 2017, Volume and Issue: 8(3), P. e2696 - e2696

Published: March 23, 2017

Abstract The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development a iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form (SAD). Our chemically defined highly efficient provides >95% homogeneous populations astrocytes within 30 days differentiation cortical neural progenitor cells (NPCs). All expressed functional markers including glial fibrillary acidic protein (GFAP), excitatory amino acid transporter-1 (EAAT1), S100B glutamine synthetase (GS) comparable to that adult vivo. However, derived both SAD FAD exhibit pronounced phenotype, significantly less complex morphological appearance, overall atrophic profiles abnormal localisation key astroglial markers. Furthermore, NPCs identical did not show any differences, therefore, validating remodelled are as result defective intermediates. This work only presents novel study mechanisms , but also an ideal platform for further interrogation early autonomous events possibility identification therapeutic targets treatment AD.

Language: Английский

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Infection of Fungi and Bacteria in Brain Tissue From Elderly Persons and Patients With Alzheimer’s Disease

Frontiers in Aging Neuroscience, Journal Year: 2018, Volume and Issue: 10

Published: May 24, 2018

Alzheimer's disease (AD) is the leading cause of dementia in elderly people. The etiology this remains a matter intensive research many laboratories. We have advanced idea that disseminated fungal infection contributes to AD. Thus, we demonstrated proteins and DNA are present nervous tissue from AD patients. More recently, reported bacterial infections can accompany these mycoses, suggesting polymicrobial exist brains. In study, examined brain patients control subjects by immunohistochemistry. addition, documented species regions next-generation sequencing (NGS). Our results analysis ten reveal variety species, although some were more prominent than others. genera prevalent Alternaria, Botrytis, Candida Malassezia. also compared with those found younger subjects. One most was Fusarium. Principal component clearly indicated fungi frontal cortex samples brains clustered together differed equivalent Regarding infection, phylum Proteobacteria both controls, followed Firmicutes, Actinobacteria Bacteroides. At family level, Burkholderiaceae Staphylococcaceae exhibited higher percentages These findings could be interest guide targeted antimicrobial therapy for Moreover, microbial each patient may constitute basis better understanding evolution severity clinical symptoms patient.

Language: Английский

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