scholarly journals Ceramides in Alzheimer’s Disease: Key Mediators of Neuronal Apoptosis Induced by Oxidative Stress and AβAccumulation

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Maja Jazvinšćak Jembrek ◽  
Patrick R. Hof ◽  
Goran Šimić
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Apoptosis ◽  
Neurodegenerative Disorder ◽  
Neuronal Degeneration ◽  
Sphingolipid Metabolism ◽  
Cytochrome C Release ◽  
Biochemical Alterations

Alzheimer’s disease (AD), the most common chronic and progressive neurodegenerative disorder, is characterized by extracellular deposits of amyloidβ-peptides (Aβ) and intracellular deposits of hyperphosphorylated tau (phospho-tau) protein. Ceramides, the major molecules of sphingolipid metabolism and lipid second messengers, have been associated with AD progression and pathology via Aβgeneration. Enhanced levels of ceramides directly increase Aβthrough stabilization ofβ-secretase, the key enzyme in the amyloidogenic processing of Aβprecursor protein (APP). As a positive feedback loop, the generated oligomeric and fibrillar Aβinduces a further increase in ceramide levels by activating sphingomyelinases that catalyze the catabolic breakdown of sphingomyelin to ceramide. Evidence also supports important role of ceramides in neuronal apoptosis. Ceramides may initiate a cascade of biochemical alterations, which ultimately leads to neuronal death by diverse mechanisms, including depolarization and permeabilization of mitochondria, increased production of reactive oxygen species (ROS), cytochrome c release, Bcl-2 depletion, and caspase-3 activation, mainly by modulating intracellular signalling, particularly along the pathways related to Akt/PKB kinase and mitogen-activated protein kinases (MAPKs). This review summarizes recent findings related to the role of ceramides in oxidative stress-driven neuronal apoptosis and interplay with Aβin the cascade of events ending in neuronal degeneration.

Oxidative Stress Targeting Amyloid Beta Accumulation and Clearance in Alzheimer’s Disease: Insight into Pathological Mechanisms and Therapeutic Strategies

2020 ◽  
Vol 9 (1) ◽  
pp. 22-42
Author(s):  
Sunpreet Kaur ◽  
Puneet Kumar ◽  
Shamsher Singh
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neurodegenerative Disorder ◽  
Acetylcholinesterase Inhibitors ◽  
The Elderly ◽  
Biochemical Alterations ◽  
App Trafficking ◽  
Copper Aluminum

Background: Alzheimer’s disease is the most common neurodegenerative disorder affecting the elderly population and emerges as a leading challenge for the scientific research community. The wide pathological aspects of AD made it a multifactorial disorder and even after long time it’s difficult to treat due to unexplored etiological factors. Methods: The etiogenesis of AD includes mitochondrial failure, gut dysbiosis, biochemical alterations but deposition of amyloid-beta plaques and neurofibrillary tangles are implicated as major hallmarks of neurodegeneration in AD. The aggregates of these proteins disrupt neuronal signaling, enhance oxidative stress and reduce activity of various cellular enzymes which lead to neurodegeneration in the cerebral cortex, neocortex and hippocampus. The metals like copper, aluminum are involved in APP trafficking and promote amyloidbeta aggregation. Similarly, disturbed ubiquitin proteasomal system, autophagy and amyloid- beta clearance mechanisms exert toxic insult in the brain. Result and conclusion : The current review explored the role of oxidative stress in disruption of amyloid homeostasis which further leads to amyloid-beta plaque formation and subsequent neurodegeneration in AD. Presently, management of AD relies on the use of acetylcholinesterase inhibitors, antioxidants and metal chelators but they are not specific measures. Therefore, in this review, we have widely cited the various pathological mechanisms of AD as well as possible therapeutic targets.

scholarly journals Role of Methylglyoxal in Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Cristina Angeloni ◽  
Laura Zambonin ◽  
Silvana Hrelia
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Advanced Glycation ◽  
Hyperphosphorylated Tau Protein ◽  
Glycation End Products ◽  
And Oxidative Stress ◽  
Endogenous Process

Alzheimer’s disease is the most common and lethal neurodegenerative disorder. The major hallmarks of Alzheimer’s disease are extracellular aggregation of amyloidβpeptides and, the presence of intracellular neurofibrillary tangles formed by precipitation/aggregation of hyperphosphorylated tau protein. The etiology of Alzheimer’s disease is multifactorial and a full understanding of its pathogenesis remains elusive. Some years ago, it has been suggested that glycation may contribute to both extensive protein cross-linking and oxidative stress in Alzheimer’s disease. Glycation is an endogenous process that leads to the production of a class of compounds known as advanced glycation end products (AGEs). Interestingly, increased levels of AGEs have been observed in brains of Alzheimer’s disease patients. Methylglyoxal, a reactive intermediate of cellular metabolism, is the most potent precursor of AGEs and is strictly correlated with an increase of oxidative stress in Alzheimer’s disease. Many studies are showing that methylglyoxal and methylglyoxal-derived AGEs play a key role in the etiopathogenesis of Alzheimer's disease.

Microglia in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Patrick Süß ◽  
Johannes C.M. Schlachetzki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Amyloid Β ◽  
Disease Stage ◽  
Disease Modifying Therapy ◽  
Transcriptomic Signature

: Alzheimer’s Disease (AD) is the most frequent neurodegenerative disorder. Although proteinaceous aggregates of extracellular Amyloid-β (Aβ) and intracellular hyperphosphorylated microtubule- associated tau have long been identified as characteristic neuropathological hallmarks of AD, a disease- modifying therapy against these targets has not been successful. An emerging concept is that microglia, the innate immune cells of the brain, are major players in AD pathogenesis. Microglia are longlived tissue-resident professional phagocytes that survey and rapidly respond to changes in their microenvironment. Subpopulations of microglia cluster around Aβ plaques and adopt a transcriptomic signature specifically linked to neurodegeneration. A plethora of molecules and pathways associated with microglia function and dysfunction has been identified as important players in mediating neurodegeneration. However, whether microglia exert either beneficial or detrimental effects in AD pathology may depend on the disease stage. : In this review, we summarize the current knowledge about the stage-dependent role of microglia in AD, including recent insights from genetic and gene expression profiling studies as well as novel imaging techniques focusing on microglia in human AD pathology and AD mouse models.

scholarly journals Neuroprotective Mechanisms of Resveratrol in Alzheimer’s Disease: Role of SIRT1

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Bruno Alexandre Quadros Gomes ◽  
João Paulo Bastos Silva ◽  
Camila Fernanda Rodrigues Romeiro ◽  
Sávio Monteiro dos Santos ◽  
Caroline Azulay Rodrigues ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Vital Role ◽  
Hippocampal Damage ◽  
Neuroprotective Effects ◽  
Amyloid A ◽  
Silent Information Regulator 1 ◽  
Anti Inflammatory

Alzheimer’s disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence ofβ-amyloid (Aβ) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aβpeptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti-inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aβpeptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator-1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti-inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti-inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti-inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.

scholarly journals Investigating the role of neuronal oxidative stress in early Alzheimer’s disease pathology

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Morgan K. Foret ◽  
Sonia Do Carmo ◽  
Lindsay A. Welikovitch ◽  
Chiara Orciani ◽  
A. Claudio Cuello
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Alzheimer’S Disease

The Key Role of Oxidative Stress in Alzheimer's Disease

2007 ◽  
pp. 267-281 ◽  
Author(s):  
Paula I. Moreira ◽  
Akihiko Nunomura ◽  
Kazuhiro Honda ◽  
Gjumrakch Aliev ◽  
Gemma Casadesus ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease
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