Acetylated Tau Protein: A New Piece in the Puzzle between Brain Ischemia and Alzheimer’s Disease

Pluta, Ryszard; Januszewski, Sławomir; Jabłoński, Mirosław

doi:10.3390/ijms23169174

Cited by 4 publications

(6 citation statements)

References 93 publications

(212 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The increase in the level of total tau protein, which was assessed by brain microdialysis after ischemia, has to be also mentioned [50], and this increase correlated with immunostaining [51] and with our study on tau protein gene expression. Numerous studies have shown that after ischemia, tau protein is hyperphosphorylated in neurons and is closely related to the development of their death through the mechanism of apoptosis [52,53]. Finally, hyperphosphorylation of tau protein causes the formation of paired helical filaments after brain ischemia [54], neurofibrillary tangles-like [55], and neurofibrillary tangles [33,34] characteristic of AD.…”

Section: Discussionmentioning

confidence: 99%

Alpha-, Beta-, and Gamma-Secretase, Amyloid Precursor Protein, and Tau Protein Genes in the Hippocampal CA3 Subfield in an Ischemic Model of Alzheimer’s Disease with Survival up to 2 Years

Czuczwar,

Kocki,

Miziak

et al. 2024

JAD

Self Cite

View full text Add to dashboard Cite

Background: Understanding the phenomena underlying the non-selective susceptibility to ischemia of pyramidal neurons in the CA3 is important from the point of view of elucidating the mechanisms of memory loss and the development of dementia. Objective: The aim of the study was to investigate changes in genes expression of amyloid precursor protein, its cleaving enzymes and tau protein in CA3 post-ischemia with survival of 12–24 months. Methods: We used an ischemic model of Alzheimer’s disease to study the above genes using an RT-PCR protocol. Results: The expression of the amyloid precursor protein gene was above the control values at all times post-ischemia. The expression of the α -secretase gene also exceeded the control values post-ischemia. The expression of the β -secretase gene increased 12 and 24 months post-ischemia, and 18 months was below control values. Presenilin 1 and 2 genes expression was significantly elevated at all times post-ischemia. Also, tau protein gene expression was significantly elevated throughout the observation period, and peak gene expression was present 12 months post-ischemia. Conclusions: The study suggests that the genes studied are involved in the non-amyloidogenic processing of amyloid precursor protein. Additionally data indicate that brain ischemia with long-term survival causes damage and death of pyramidal neurons in the CA3 area of the hippocampus in a modified tau protein-dependent manner. Thus defining a new and important mechanism of pyramidal neuronal death in the CA3 area post-ischemia. In addition expression of tau protein gene modification after brain ischemia is useful in identifying ischemic mechanisms occurring in Alzheimer’s disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Alpha-, Beta-, and Gamma-Secretase, Amyloid Precursor Protein, and Tau Protein Genes in the Hippocampal CA3 Subfield in an Ischemic Model of Alzheimer’s Disease with Survival up to 2 Years

Czuczwar,

Kocki,

Miziak

et al. 2024

JAD

Self Cite

View full text Add to dashboard Cite

show abstract

“…The increase in the level of total tau protein, which was assessed by brain microdialysis after ischemia, has to be also mentioned [29], and this increase correlated with immunostaining [30] and with our study of tau protein gene expression. Numerous studies have shown that after ischemia, tau protein is hyperphosphorylated in neurons and is closely related to the development of their death through the mechanism of apoptosis [31,32]. Finally, hyperphosphorylation causes the formation of paired helical filaments after cerebral ischemia [33], neurofibrillary tangles-like [34], and neurofibrillary tangles [35,36] characteristic of Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 99%

Alterations in the amyloid protein precursor, α-secretase, β-secretase, presenilins and tau protein Genes in the CA3 Area of the Hippocampus in a 2-Year Ischemic Model of Alzheimer’s Disease

Czuczwar,

Kocki,

Miziak

et al. 2023

Preprint

View full text Add to dashboard Cite

Understanding the phenomena underlying the non-selective susceptibility to ischemia of py-ramidal neurons in the CA3 area of the hippocampus is important from the point of view of elu-cidating the mechanisms of memory loss and the development of post-ischemic dementia. We used an ischemic model of Alzheimer's disease to study changes in amyloid protein precursor gene expression, its cleavage enzymes and tau protein in the CA3 area of the hippocampus af-ter a 10-minute brain ischemia with 12, 18, and 24-month survival. Quantitative reverse tran-scriptase PCR assay showed that the expression of all the genes that contribute to amyloid pro-duction was dysregulated within 2 years in the CA3 area of the hippocampus after ischemia. The expression of the amyloid protein precursor gene was above the control values at all times of the study. The expression of the α-secretase gene also exceeded the control values throughout the study. In contrast, the expression of the β-secretase gene reaching its maximum increase 12 months after ischemia, was below control values after 18 months and again above control values after 24 months of survival. Presenilin 1 and 2 gene expression was significantly elevated throughout the follow-up period, with peak expression of both genes occurring 12 months after ischemia. This suggests that the genes studied are involved in the non-amyloidogenic processing of amyloid protein precursor. Also, tau protein gene expression was significantly elevated throughout the observation period, and peak gene expression was present 12 months after is-chemia. Data indicate that an episode of brain ischemia with long-term survival causes damage and death of pyramidal neurons in the CA3 area of the hippocampus in a manner dependent on modified tau protein. Thus defining a new and important mechanism of pyramidal neuronal death in the CA3 area after ischemia. In addition tau protein gene modification after brain is-chemia is useful in identifying ischemic mechanisms occurring in Alzheimer's disease.

show abstract

“…This directly indicates that the neuropathological changes, including changes in the tau protein, triggered by brain ischemia are identical to those in Alzheimer's disease [29,41,107,115,[128][129][130]. In our previous studies, we assessed the expression of genes related to amyloid generation in the CA1 and CA3 areas of the hippocampus and temporal cortex [77,88]. Alzheimer's disease-associated genes such as amyloid protein precursor, β-secretase, and presenilin 1 and 2 undergo ischemic genetic programming.…”

Section: Amyloid and Tau Proteinsmentioning

confidence: 98%

“…Cerebral ischemia triggers a number of biochemical reactions at the cellular level. They encompass excitotoxicity, oxidative stress, anaerobic metabolism, cellular energy loss, cytoplasmic calcium overload, mitochondrial dysfunction, free radical production, inflammatory reactions, and amyloid and tau protein pathology [6,27,28,30,[55][56][57][68][69][70][71][72][73][74][75][76][77]. These processes generate significant pathology of neurons and neuroglial cells and eventually participate in the aggravation of blood-brain barrier dysfunction [57,71,76,[78][79][80][81][82][83][84][85][86][87][88][89][90], development of brain edema [81], and brain atrophy [27,[82][83][84], which ultimately results in irreversible brain damage [27] and dementia [84][85][86][87].…”

Section: Post-ischemic Neurodegenerative Cascade In the Brainmentioning

confidence: 99%

Apitherapy in Post-Ischemic Brain Neurodegeneration of Alzheimer’s Disease Proteinopathy: Focus on Honey and Its Flavonoids and Phenolic Acids

2023

Self Cite

View full text Add to dashboard Cite

Neurodegeneration of the brain after ischemia is a major cause of severe, long-term disability, dementia, and mortality, which is a global problem. These phenomena are attributed to excitotoxicity, changes in the blood–brain barrier, neuroinflammation, oxidative stress, vasoconstriction, cerebral amyloid angiopathy, amyloid plaques, neurofibrillary tangles, and ultimately neuronal death. In addition, genetic factors such as post-ischemic changes in genetic programming in the expression of amyloid protein precursor, β-secretase, presenilin-1 and -2, and tau protein play an important role in the irreversible progression of post-ischemic neurodegeneration. Since current treatment is aimed at preventing symptoms such as dementia and disability, the search for causative therapy that would be helpful in preventing and treating post-ischemic neurodegeneration of Alzheimer’s disease proteinopathy is ongoing. Numerous studies have shown that the high contents of flavonoids and phenolic acids in honey have antioxidant, anti-inflammatory, anti-apoptotic, anti-amyloid, anti-tau protein, anticholinesterase, serotonergic, and AMPAK activities, influencing signal transmission and neuroprotective effects. Notably, in many preclinical studies, flavonoids and phenolic acids, the main components of honey, were also effective when administered after ischemia, suggesting their possible use in promoting recovery in stroke patients. This review provides new insight into honey’s potential to prevent brain ischemia as well as to ameliorate damage in advanced post-ischemic brain neurodegeneration.

show abstract

Acetylated Tau Protein: A New Piece in the Puzzle between Brain Ischemia and Alzheimer’s Disease

Abstract: Cerebral ischemia in humans and animals is a life-threatening neuropathological event and leads to the development of dementia with the Alzheimer’s disease phenotype [...]

Cited by 4 publications

References 93 publications

Alpha-, Beta-, and Gamma-Secretase, Amyloid Precursor Protein, and Tau Protein Genes in the Hippocampal CA3 Subfield in an Ischemic Model of Alzheimer’s Disease with Survival up to 2 Years

Alpha-, Beta-, and Gamma-Secretase, Amyloid Precursor Protein, and Tau Protein Genes in the Hippocampal CA3 Subfield in an Ischemic Model of Alzheimer’s Disease with Survival up to 2 Years

Alterations in the <em>amyloid protein precursor</em>, <em>α-secretase</em>, <em>β-secretase</em>, <em>presenilins</em> and <em>tau protein</em> Genes in the CA3 Area of the Hippocampus in a 2-Year Ischemic Model of Alzheimer’s Disease

Apitherapy in Post-Ischemic Brain Neurodegeneration of Alzheimer’s Disease Proteinopathy: Focus on Honey and Its Flavonoids and Phenolic Acids

Contact Info

Product

Resources

About