Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease

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

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Neuronal Cell Death

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(2), P. 813 - 880

Published: Feb. 28, 2018

Neuronal cell death occurs extensively during development and pathology, where it is especially important because of the limited capacity adult neurons to proliferate or be replaced. The concept used simple as there were just two three types, so we had work out which type was involved in our particular pathology then block it. However, now know that are at least a dozen ways for die, blocking mechanism may not prevent from dying, non-neuronal cells also contribute neuronal death. We review here mechanisms by intrinsic extrinsic apoptosis, oncosis, necroptosis, parthanatos, ferroptosis, sarmoptosis, autophagic death, autosis, autolysis, paraptosis, pyroptosis, phagoptosis, mitochondrial permeability transition. next explore development, those induced axotomy, aberrant cell-cycle reentry, glutamate (excitoxicity oxytosis), loss connected neurons, aggregated proteins unfolded protein response, oxidants, inflammation, microglia. reassess forms occur stroke Alzheimer’s disease, most pathologies involving discuss why has been difficult pinpoint involved, if matters, molecular overlap interplay between subroutines, therapeutic implications these multiple overlapping

Language: Английский

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History and progress of hypotheses and clinical trials for Alzheimer’s disease

Signal Transduction and Targeted Therapy, Journal Year: 2019, Volume and Issue: 4(1)

Published: Aug. 23, 2019

Abstract Alzheimer’s disease (AD) is a neurodegenerative characterized by progressive memory loss along with neuropsychiatric symptoms and decline in activities of daily life. Its main pathological features are cerebral atrophy, amyloid plaques, neurofibrillary tangles the brains patients. There various descriptive hypotheses regarding causes AD, including cholinergic hypothesis, tau propagation mitochondrial cascade calcium homeostasis neurovascular inflammatory metal ion lymphatic system hypothesis. However, ultimate etiology AD remains obscure. In this review, we discuss related clinical trials. Wealthy puzzles lessons have made it possible to develop explanatory theories identify potential strategies for therapeutic interventions AD. The combination hypometabolism autophagy deficiency likely be causative factor We further propose that fluoxetine, selective serotonin reuptake inhibitor, has treat

Language: Английский

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Current state of Alzheimer’s fluid biomarkers

Acta Neuropathologica, Journal Year: 2018, Volume and Issue: 136(6), P. 821 - 853

Published: Nov. 28, 2018

Alzheimer's disease (AD) is a progressive neurodegenerative with complex and heterogeneous pathophysiology. The number of people living AD predicted to increase; however, there are no disease-modifying therapies currently available none have been successful in late-stage clinical trials. Fluid biomarkers measured cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development establishing personalized medicine approach diagnosis treatment. Biomarkers used programmes should be qualified specific context use (COU). These COUs include, but not limited to, subject/patient selection, assessment state and/or prognosis, mechanism action, dose optimization, response monitoring, efficacy maximization, toxicity/adverse reactions identification minimization. core CSF Aβ42, t-tau, p-tau recognized by research guidelines their diagnostic utility being considered qualification subject selection However, need better understand potential other COUs, as well identify additional reflecting aspects Several novel proposed, role pathology yet validated. In this review, we summarize some the pathological mechanisms implicated sporadic highlight data several established (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, NF-L) associated each mechanism. We discuss biomarker.

Language: Английский

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Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases

Frontiers in Chemistry, Journal Year: 2023, Volume and Issue: 11

Published: May 10, 2023

Introduction: Free radicals are reactive oxygen species that constantly circulate through the body and occur as a side effect of many reactions take place in human body. Under normal conditions, they removed from by antioxidant processes. If these natural mechanisms disrupted, accumulate excess contribute to development diseases. Methodology: Relevant recent information on oxidative stress, free radicals, species, synthetic antioxidants was collected researching electronic databases such PubMed / Medline, Web Science, Science Direct. Results: According analysed studies, this comprehensive review provided update their impact pathophysiology Discussion: To counteract condition must be external sources supplement defense mechanism internally. Because therapeutic potential origin, medicinal plants have been reported main source phytocompounds. Some non-enzymatic phytocompounds flavonoids, polyphenols, glutathione, along with some vitamins possess strong activities vivo vitro studies. Thus, present describes, brief, overview stress-directed cellular damage unction dietary management different The limitations correlating activity foods health were also discussed.

Language: Английский

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The Amyloid Cascade Hypothesis in Alzheimer’s Disease: It’s Time to Change Our Mind

Current Neuropharmacology, Journal Year: 2017, Volume and Issue: 15(6)

Published: July 31, 2017

Since its discovery in 1984, the beta amyloid peptide has treaded boards of neurosciences as star molecule Alzheimer’s disease pathogenesis. In last decade, however, this vision been challenged by evidence-based medicine showing almost complete failure clinical trials that experimented anti-amyloid therapies with great hopes. Moreover, data have accumulated which clearly indicate small plays a key role physiological processes memory formation. present review, we will discuss different aspects cascade hypothesis, highlighting pros and cons, analyse results therapeutic approaches attempted to date should change direction research future. Keywords: Alzheimer's disease, amyloid, trials, LTP, memory, therapy.

Language: Английский

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Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 10, 2021

Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long (lncRNAs), and circular (circRNAs), are closely related variety biological functional aspects human health. When the exosomal ncRNAs undergo tissue-specific changes due diverse internal or external disorders, they can cause tissue dysfunction, aging, diseases. In this review, we comprehensively discuss underlying regulatory mechanisms exosomes in addition, explore current knowledge on roles miRNAs, lncRNAs, circRNAs health diseases, including cancers, metabolic neurodegenerative cardiovascular autoimmune infectious determine their potential implication biomarker identification therapeutic exploration.

Language: Английский

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Synaptic basis of Alzheimer’s disease: Focus on synaptic amyloid beta, P-tau and mitochondria

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 65, P. 101208 - 101208

Published: Nov. 4, 2020

Language: Английский

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Dysfunction of NMDA receptors in Alzheimer’s disease

Neurological Sciences, Journal Year: 2016, Volume and Issue: 37(7), P. 1039 - 1047

Published: March 12, 2016

N-methyl-d-aspartate receptors (NMDARs) play a pivotal role in the synaptic transmission and plasticity thought to underlie learning memory. NMDARs activation has been recently implicated Alzheimer’s disease (AD) related dysfunction. Synaptic are neuroprotective, whereas overactivation of located outside synapse cause loss mitochondrial membrane potential cell death. dysfunction glutamatergic tripartite synapse, comprising presynaptic postsynaptic neurons glial cells, is directly involved AD. This review discusses that both beta-amyloid (Aβ) tau perturb functioning including alterations glutamate release, astrocytic uptake, receptor signaling. Particular emphasis given as possible convergence point for Aβ toxicity reversible stages AD through preventive and/or disease-modifying therapeutic strategies.

Language: Английский

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Oxidative stress in alzheimer’s disease: A review on emergent natural polyphenolic therapeutics

Complementary Therapies in Medicine, Journal Year: 2019, Volume and Issue: 49, P. 102294 - 102294

Published: Dec. 31, 2019

Language: Английский

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