scholarly journals Cross-Talk between Amyloid, Tau Protein and Free Radicals in Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 146
Author(s):  
Ryszard Pluta ◽  
Jacek Kiś ◽  
Sławomir Januszewski ◽  
Mirosław Jabłoński ◽  
Stanisław J. Czuczwar
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Damage ◽  
Free Radicals ◽  
Brain Ischemia ◽  
Tau Protein ◽  
Dna Damage And Repair ◽  
Ischemic Brain ◽  
Remarkable Progress

Recent years have seen remarkable progress in research into free radicals oxidative stress, particularly in the context of post-ischemic recirculation brain injury. Oxidative stress in post-ischemic tissues violates the integrity of the genome, causing DNA damage, death of neuronal, glial and vascular cells, and impaired neurological outcome after brain ischemia. Indeed, it is now known that DNA damage and repair play a key role in post-stroke white and gray matter remodeling, and restoring the integrity of the blood-brain barrier. This review will present one of the newly characterized mechanisms that emerged with genomic and proteomic development that led to brain ischemia to a new level of post-ischemic neuropathological mechanisms, such as the presence of amyloid plaques and the development of neurofibrillary tangles, which further exacerbate oxidative stress. Finally, we hypothesize that modified amyloid and the tau protein, along with the oxidative stress generated, are new key elements in the vicious circle important in the development of post-ischemic neurodegeneration in a type of Alzheimer’s disease proteinopathy.

scholarly journals Brain Ischemia as a Prelude to Alzheimer's Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Ryszard Pluta ◽  
Sławomir Januszewski ◽  
Stanisław J. Czuczwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Injury ◽  
White Matter ◽  
Brain Ischemia ◽  
Tau Protein ◽  
Ischemia Reperfusion ◽  
Acute Stage ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

Transient ischemic brain injury causes massive neuronal death in the hippocampus of both humans and animals. This was accompanied by progressive atrophy of the hippocampus, brain cortex, and white matter lesions. Furthermore, it has been noted that neurodegenerative processes after an episode of ischemia-reperfusion in the brain can continue well-beyond the acute stage. Rarefaction of white matter was significantly increased in animals at 2 years following ischemia. Some rats that survived 2 years after ischemia developed severe brain atrophy with dementia. The profile of post-ischemic brain neurodegeneration shares a commonality with neurodegeneration in Alzheimer's disease. Furthermore, post-ischemic brain injury is associated with the deposition of folding proteins, such as amyloid and tau protein, in the intracellular and extracellular space. Recent studies on post-ischemic brain neurodegeneration have revealed the dysregulation of Alzheimer's disease-associated genes such as amyloid protein precursor, α-secretase, β-secretase, presenilin 1, presenilin 2, and tau protein. The latest data demonstrate that Alzheimer's disease-related proteins and their genes play a key role in the development of post-ischemic brain neurodegeneration with full-blown dementia in disease types such as Alzheimer's. Ongoing interest in the study of brain ischemia has provided evidence showing that ischemia may be involved in the development of the genotype and phenotype of Alzheimer's disease, suggesting that brain ischemia can be considered as a useful model for understanding the mechanisms responsible for the initiation of Alzheimer's disease.

scholarly journals Neuroprotective and Neurological/Cognitive Enhancement Effects of Curcumin after Brain Ischemia Injury with Alzheimer’s Disease Phenotype

2018 ◽  
Vol 19 (12) ◽  
pp. 4002 ◽  
Author(s):  
Ryszard Pluta ◽  
Marzena Ułamek-Kozioł ◽  
Stanisław Czuczwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Injury ◽  
Brain Ischemia ◽  
Tau Protein ◽  
Protective Action ◽  
Ischemic Brain Injury ◽  
Disease Phenotype ◽  
Ischemic Brain ◽  
Ca1 Region

In recent years, ongoing interest in ischemic brain injury research has provided data showing that ischemic episodes are involved in the development of Alzheimer’s disease-like neuropathology. Brain ischemia is the second naturally occurring neuropathology, such as Alzheimer’s disease, which causes the death of neurons in the CA1 region of the hippocampus. In addition, brain ischemia was considered the most effective predictor of the development of full-blown dementia of Alzheimer’s disease phenotype with a debilitating effect on the patient. Recent knowledge on the activation of Alzheimer’s disease-related genes and proteins—e.g., amyloid protein precursor and tau protein—as well as brain ischemia and Alzheimer’s disease neuropathology indicate that similar processes contribute to neuronal death and disintegration of brain tissue in both disorders. Although brain ischemia is one of the main causes of death in the world, there is no effective therapy to improve the structural and functional outcomes of this disorder. In this review, we consider the promising role of the protective action of curcumin after ischemic brain injury. Studies of the pharmacological properties of curcumin after brain ischemia have shown that curcumin has several therapeutic properties that include anti-excitotoxic, anti-oxidant, anti-apoptotic, anti-hyperhomocysteinemia and anti-inflammatory effects, mitochondrial protection, as well as increasing neuronal lifespan and promoting neurogenesis. In addition, curcumin also exerts anti-amyloidogenic effects and affects the brain’s tau protein. These results suggest that curcumin may be able to serve as a potential preventive and therapeutic agent in neurodegenerative brain disorders.

scholarly journals The Bewildering Effect of AMPK Activators in Alzheimer’s Disease: Review of the Current Evidence

2020 ◽  
Vol 2020 ◽  
pp. 1-18 ◽  
Author(s):  
Brhane Teklebrhan Assefa ◽  
Gebrehiwot Gebremedhin Tafere ◽  
Dawit Zewdu Wondafrash ◽  
Meles Tekie Gidey
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaque ◽  
Current Evidence ◽  
Negative Effects ◽  
Disease Modifying Therapy ◽  
Tau Aggregation ◽  
And Oxidative Stress ◽  
Remarkable Progress

Alzheimer’s disease is a multifactorial neurodegenerative disease characterized by progressive cognitive dysfunction. It is the most common form of dementia. The pathologic hallmarks of the disease include extracellular amyloid plaque, intracellular neurofibrillary tangles, and oxidative stress, to mention some of them. Despite remarkable progress in the understanding of the pathogenesis of the disease, drugs for cure or disease-modifying therapy remain somewhere in the distance. From recent time, the signaling molecule AMPK is gaining enormous attention in the AD drug research. AMPK is a master regulator of cellular energy metabolism, and recent pieces of evidence show that perturbation of its function is highly ascribed in the pathology of AD. Several drugs are known to activate AMPK, but their effect in AD remains to be controversial. In this review, the current shreds of evidence on the effect of AMPK activators in Aβ accumulation, tau aggregation, and oxidative stress are addressed. Positive and negative effects are reported with regard to Aβ and tauopathy but only positive in oxidative stress. We also tried to dissect the molecular interplays where the bewildering effects arise from.

scholarly journals The Many Faces of Post-Ischemic Tau Protein in Brain Neurodegeneration of the Alzheimer’s Disease Type

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2213
Author(s):  
Ryszard Pluta ◽  
Stanisław J. Czuczwar ◽  
Sławomir Januszewski ◽  
Mirosław Jabłoński
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Tau Protein ◽  
Ischemia Reperfusion ◽  
Disease Type ◽  
Dependent Manner ◽  
Ischemic Brain ◽  
The Brain

Recent data suggest that post-ischemic brain neurodegeneration in humans and animals is associated with the modified tau protein in a manner typical of Alzheimer’s disease neuropathology. Pathological changes in the tau protein, at the gene and protein level due to cerebral ischemia, can lead to the development of Alzheimer’s disease-type neuropathology and dementia. Some studies have shown increased tau protein staining and gene expression in neurons following ischemia-reperfusion brain injury. Recent studies have found the tau protein to be associated with oxidative stress, apoptosis, autophagy, excitotoxicity, neuroinflammation, blood-brain barrier permeability, mitochondrial dysfunction, and impaired neuronal function. In this review, we discuss the interrelationship of these phenomena with post-ischemic changes in the tau protein in the brain. The tau protein may be at the intersection of many pathological mechanisms due to severe neuropathological changes in the brain following ischemia. The data indicate that an episode of cerebral ischemia activates the damage and death of neurons in the hippocampus in a tau protein-dependent manner, thus determining a novel and important mechanism for the survival and/or death of neuronal cells following ischemia. In this review, we update our understanding of proteomic and genomic changes in the tau protein in post-ischemic brain injury and present the relationship between the modified tau protein and post-ischemic neuropathology and present a positive correlation between the modified tau protein and a post-ischemic neuropathology that has characteristics of Alzheimer’s disease-type neurodegeneration.

scholarly journals Participation of Amyloid and Tau Protein in Neuronal Death and Neurodegeneration after Brain Ischemia

2020 ◽  
Vol 21 (13) ◽  
pp. 4599 ◽  
Author(s):  
Ryszard Pluta ◽  
Marzena Ułamek-Kozioł ◽  
Sławomir Januszewski ◽  
Stanisław J. Czuczwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Ischemia ◽  
Tau Protein ◽  
Neuronal Cells ◽  
Current Evidence ◽  
Amyloid Protein ◽  
Protein Precursor ◽  
Amyloid Protein Precursor ◽  
Related Proteins

Current evidence indicates that postischemic brain injury is associated with the accumulation of folding proteins, such as amyloid and tau protein, in the intra- and extracellular spaces of neuronal cells. In this review, we summarize protein changes associated with Alzheimer’s disease and their gene expression (amyloid protein precursor and tau protein) after brain ischemia, and their roles in the postischemic period. Recent advances in understanding the postischemic mechanisms in development of neurodegeneration have revealed dysregulation of amyloid protein precursor, α-, β- and γ-secretase and tau protein genes. Reduced expression of the α-secretase gene after brain ischemia with recirculation causes neuronal cells to be less resistant to injury. We present the latest data that Alzheimer’s disease-related proteins and their genes play a crucial role in postischemic neurodegeneration. Understanding the underlying processes of linking Alzheimer’s disease-related proteins and their genes in development of postischemic neurodegeneration will provide the most significant goals to date for therapeutic development.

Associations between DNA Damage, DNA Base Excision Repair Gene Variability and Alzheimer's Disease Risk

2016 ◽  
Vol 41 (3-4) ◽  
pp. 152-171 ◽  
Author(s):  
Dominik Kwiatkowski ◽  
Piotr Czarny ◽  
Monika Toma ◽  
Natalia Jurkowska ◽  
Agnieszka Sliwinska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Damage ◽  
Dna Repair ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Lesions ◽  
Polymorphic Variants ◽  
Base Excision

Background: Increased oxidative damage to DNA is one of the pathways involved in Alzheimer's disease (AD). Insufficient base excision repair (BER) is in part responsible for increased oxidative DNA damage. The aim of the present study was to assess the effect of polymorphic variants of BER-involved genes and the peripheral markers of DNA damage and repair in patients with AD. Material and Methods: Comet assays and TaqMan probes were used to assess DNA damage, BER efficiency and polymorphic variants of 12 BER genes in blood samples from 105 AD patients and 130 controls. The DNA repair efficacy (DRE) was calculated according to a specific equation. Results: The levels of endogenous and oxidative DNA damages were higher in AD patients than controls. The polymorphic variants of XRCC1 c.580C>T XRCC1 c.1196A>G and OGG1 c.977C>G are associated with increased DNA damage in AD. Conclusion: Our results show that oxidative stress and disturbances in DRE are particularly responsible for the elevated DNA lesions in AD. The results suggest that oxidative stress and disruption in DNA repair may contribute to increased DNA damage in AD patients and risk of this disease. In addition, disturbances in DRE may be associated with polymorphisms of OGG1 and XRCC1.

scholarly journals Papel del estrés oxidativo en el desarrollo del deterioro cognitivo y su progresión a enfermedad de Alzheimer

2019 ◽  
pp. 14-22
Author(s):  
Josue CRUZ-RODRÍGUEZ ◽  
Gabriel BETANZOS-CABRERA ◽  
Brenda Hildeliza CAMACHO-DÍAZ ◽  
María Araceli ORTIZ-RODRÍGUEZ
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Free Radicals ◽  
Neuronal Death ◽  
Energy Demand ◽  
Brain Aging ◽  
Neurological Diseases ◽  
Amyloid Peptide

This review aims to provide scientific evidence of the role of oxidative stress in the development of cognitive impairment and its progression to Alzheimer's disease. Oxidative stress originates when there is an uncontrolled production of free radicals that disrupts the balance between oxidants and antioxidants, favoring oxidants. It has been associated with oxidative stress with the pathogenesis of brain aging, cognitive impairment and some neurological diseases. The cells of the central nervous system produce a high amount of free radicals since their energy demand is high, this coupled with a low antioxidant capacity, favors the appearance of a pro-oxidant environment that contributes to neurodegeneration and neuronal death. Alzheimer's disease is the most frequent form of dementia, it is characterized by neurodegenerative changes that occur with cognitive impairment, progressive impairment of memory and thought, until preventing the performance of daily life activities. Neuropathologically, it is characterized by the presence of extracellular deposits of β-amyloid peptide in the form of neurofibrillar plaques and clews; lesions capable of generating damage and neuronal death that lead to cognitive failure through the generation of more free radicals

scholarly journals Oxidative DNA Damage Signalling in Neural Stem Cells in Alzheimer’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Marcelina Kieroń ◽  
Cezary Żekanowski ◽  
Anna Falk ◽  
Michalina Wężyk
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Dna Damage ◽  
Neural Stem Cells ◽  
Adult Neurogenesis ◽  
Oxidative Dna Damage ◽  
Signalling Pathways ◽  
Amyloid A

The main pathological symptoms of Alzheimer’s disease (AD) are β-amyloid (Aβ) lesions and intracellular neurofibrillary tangles of hyperphosphorylated tau protein. Unfortunately, existing symptomatic therapies targeting Aβ and tau remain ineffective. In addition to these pathogenic factors, oxidative DNA damage is one of the major threats to newborn neurons. It is necessary to consider in detail what causes neurons to be extremely susceptible to oxidative damage, especially in the early stages of development. Accordingly, the regulation of redox status is crucial for the functioning of neural stem cells (NSCs). The redox-dependent balance, of NSC proliferation and differentiation and thus the neurogenesis process, is controlled by a series of signalling pathways. One of the most important signalling pathways activated after oxidative stress is the DNA damage response (DDR). Unfortunately, our understanding of adult neurogenesis in AD is still limited due to the research material used (animal models or post-mortem tissue), providing inconsistent data. Now, thanks to the advances in cellular reprogramming providing patient NSCs, it is possible to fill this gap, which becomes urgent in the light of the potential of their therapeutic use. Therefore, a decent review of redox signalling in NSCs under physiological and pathological conditions is required. At this moment, we attempt to integrate knowledge on the influence of oxidative stress and DDR signalling in NSCs on adult neurogenesis in Alzheimer’s disease.

scholarly journals Porphyromonas Gingivalis May Seek the Alzheimer’s Disease Brain to Acquire Iron from Its Surplus

2021 ◽  
Vol 5 (1) ◽  
pp. 79-86
Author(s):  
Ingar Olsen
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radicals ◽  
Porphyromonas Gingivalis ◽  
Amyloid Β ◽  
Iron Chelators ◽  
Brain Areas ◽  
Beneficial Effects ◽  
The Brain

Iron accumulates in the brain of subjects with Alzheimer’s disease (AD). Here it promotes the aggregation of amyloid-β plaques in which it is abundant. Iron induces amyloid-β neurotoxicity by damaging free radicals and causing oxidative stress in brain areas with neurodegeneration. It can also bind to tau in AD and enhance the toxicity of tau through co-localization with neurofibrillary tangles and induce accumulation of these tangles. Porphyromonas gingivalis is a key oral pathogen in the widespread biofilm-induced disease “chronic” periodontitis, and recently, has been suggested to have an important role in the pathogenesis of AD. P. gingivalis has an obligate requirement for iron. The current paper suggests that P. gingivalis seeks the AD brain, where it has been identified, to satisfy this need. If this is correct, iron chelators binding iron could have beneficial effects in the treatment of AD. Indeed, studies from both animal AD models and humans with AD have indicated that iron chelators, e.g., lactoferrin, can have such effects. Lactoferrin can also inhibit P. gingivalis growth and proteinases and its ability to form biofilm.

Sign in / Sign up

Export Citation Format

Share Document