Marzena Ułamek-Kozioł
Polish Academy of Sciences
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Featured researches published by Marzena Ułamek-Kozioł.
Molecular Neurobiology | 2013
Ryszard Pluta; Mirosław Jabłoński; Marzena Ułamek-Kozioł; Janusz Kocki; Judyta Brzozowska; Sławomir Januszewski; Wanda Furmaga-Jabłońska; Anna Bogucka-Kocka; Ryszard Maciejewski; Stanisław J. Czuczwar
The study of sporadic Alzheimer’s disease etiology, now more than ever, needs an infusion of new concepts. Despite ongoing interest in Alzheimer’s disease, the basis of this entity is not yet clear. At present, the best-established and accepted “culprit” in Alzheimer’s disease pathology by most scientists is the amyloid, as the main molecular factor responsible for neurodegeneration in this disease. Abnormal upregulation of amyloid production or a disturbed clearance mechanism may lead to pathological accumulation of amyloid in brain according to the “amyloid hypothesis.” We will critically review these observations and highlight inconsistencies between the predictions of the “amyloid hypothesis” and the published data. There is still controversy over the role of amyloid in the pathological process. A question arises whether amyloid is responsible for the neurodegeneration or if it accumulates because of the neurodegeneration. Recent evidence suggests that the pathophysiology and neuropathology of Alzheimer’s disease comprises more than amyloid accumulation, tau protein pathology and finally brain atrophy with dementia. Nowadays, a handful of researchers share a newly emerged view that the ischemic episodes of brain best describe the pathogenic cascade, which eventually leads to neuronal loss, especially in hippocampus, with amyloid accumulation, tau protein pathology and irreversible dementia of Alzheimer type. The most persuasive evidences come from investigations of ischemically damaged brains of patients and from experimental ischemic brain studies that mimic Alzheimer-type dementia. This review attempts to depict what we know and do not know about the triggering factor of the Alzheimer’s disease, focusing on the possibility that the initial pathological trigger involves ischemic episodes and ischemia-induced gene dysregulation. The resulting brain ischemia dysregulates additionally expression of amyloid precursor protein and amyloid-processing enzyme genes that, in addition, ultimately compromise brain functions, leading over time to the complex alterations that characterize advanced sporadic Alzheimer’s disease. The identification of the genes involved in Alzheimer’s disease induced by ischemia will enable to further define the events leading to sporadic Alzheimer’s disease-related abnormalities. Additionally, knowledge gained from the above investigations should facilitate the elaboration of the effective treatment and/or prevention of Alzheimer’s disease.
Molecular Neurobiology | 2013
Ryszard Pluta; Wanda Furmaga-Jabłońska; Ryszard Maciejewski; Marzena Ułamek-Kozioł; Mirosław Jabłoński
Amyloid precursor protein cleavage through β- and γ-secretases produces β-amyloid peptide, which is believed to be responsible for death of neurons and dementia in Alzheimer’s disease. Levels of β- and γ-secretase are increased in sensitive areas of the Alzheimer’s disease brain, but the mechanism of this process is unknown. In this review, we prove that brain ischemia generates expression and activity of both β- and γ-secretases. These secretases are induced in association with oxidative stress following brain ischemia. Data suggest that ischemia promotes overproduction and aggregation of β-amyloid peptide in brain, which is toxic for ischemic neuronal cells. In our review, we demonstrated the role of brain ischemia as a molecular link between the β- and the γ-secretase activities and provided a molecular explanation of the possible neuropathogenesis of sporadic Alzheimer’s disease.
Neurochemical Research | 2013
Marzena Ułamek-Kozioł; Wanda Furmaga-Jabłońska; Sławomir Januszewski; Judyta Brzozowska; Małgorzata Ściślewska; Mirosław Jabłoński; Ryszard Pluta
Autophagy is a major intracellular degeneration pathway involved in the elimination and recycling of damaged organelles and long-lived proteins by lysosomes. Many of the pathological factors, which trigger neurodegenerative diseases, can perturb the autophagy activity, which is associated with misfolded protein aggregates accumulation in these disorders. Alzheimer’s disease, the first neurodegenerative disorder between dementias, is characterized by two aggregating proteins, β-amyloid peptide (plaques) and τ-protein (tangles). In Alzheimer’s disease autophagosomes dynamically form along neurites within neuronal cells and in synapses but effective clearance of these structures needs retrograde transportation towards the neuronal soma where there is a major concentration of lysosomes. Maturation of autophago-lysosomes and their retrograde trafficking are perturbed in Alzheimer’s disease, which causes a massive concentration of autophagy elements along degenerating neurites. Transportation system is disturbed along defected microtubules in Alzheimer’s disease brains. τ-protein has been found to control the stability of microtubules, however, phosphorylation of τ-protein or an increase in the total level of τ-protein can cause dysfunction of neuronal cells microtubules. Current evidence has shown that autophagy is developing in Alzheimer’s disease brains because of ineffective degradation of autophagosomes, which hold amyloid precursor protein-rich organelles and secretases important for β-amyloid peptides generation from amyloid precursor. The combination of raised autophagy induction and abnormal clearance of β-amyloid peptide-generating autophagic vacuoles creates circumstances helpful for β-amyloid peptide aggregation and accumulation in Alzheimer’s disease. However, the key role of autophagy in Alzheimer’s disease development is still under consideration today. One point of view suggests that abnormal autophagy induction causes a concentration of autophagic vacuoles rich in amyloid precursor protein, β-amyloid peptide and the elements crucial for its formation, whereas other hypothesis points to marred autophagic clearance or even decrease in autophagic effectiveness playing a role in maturation of Alzheimer’s disease. In this review we present the recent evidence linking autophagy to Alzheimer’s disease and the role of autophagic regulation in the development of full-blown Alzheimer’s disease.
Journal of Alzheimer's Disease | 2015
Janusz Kocki; Marzena Ułamek-Kozioł; Anna Bogucka-Kocka; Sławomir Januszewski; Mirosław Jabłoński; Paulina Gil-Kulik; Judyta Brzozowska; Alicja Petniak; Wanda Furmaga-Jabłońska; Jacek Bogucki; Stanisław J. Czuczwar; Ryszard Pluta
Abstract The interaction between brain ischemia and Alzheimer’s disease (AD) has been intensively investigated recently. Nevertheless, we have not yet understood the nature and mechanisms of the ischemic episodes triggering the onset of AD and how they influence its slow progression. The assumed connection between brain ischemia and the accumulation of amyloid-β (Aβ) peptide awaits to be clearly explained. In our research, we employed a rat cardiac arrest model to study the changes in gene expression of amyloid-β protein precursor (AβPP) and its cleaving enzymes, β- and γ-secretases (including presenilins) in hippocampal CA1 sector, following transient 10-min global brain ischemia. The quantitative reverse-transcriptase PCR assay demonstrated that the expression of all above genes that contribute to Aβ peptide generation was dysregulated during 30 days in postischemic hippocampal CA1 area. It suggests that studied Aβ peptide generation-related genes can be involved in AβPP metabolism, following global brain ischemia and will be useful to identify the molecular mechanisms underpinning that cerebral ischemia might be an etiological cause of AD via dysregulation of AβPP and its cleaving enzymes, β- and γ-secretases genes, and subsequently, it may increase Aβ peptide production and promote the gradual and slow development of AD neuropathology. Our data demonstrate that brain ischemia activates delayed neuronal death in hippocampus in an AβPP-dependent manner, thus defining a new and important mode of ischemic cell death.
Pharmacological Reports | 2016
Ryszard Pluta; Janusz Kocki; Marzena Ułamek-Kozioł; Anna Bogucka-Kocka; Paulina Gil-Kulik; Sławomir Januszewski; Mirosław Jabłoński; Alicja Petniak; Judyta Brzozowska; Jacek Bogucki; Wanda Furmaga-Jabłońska; Stanisław J. Czuczwar
BACKGROUND Brain ischemia may be causally related with Alzheimers disease. Probably, presenilin gene dysregulation may be associated with Alzheimers disease neuropathology. Consequently, we have examined quantitative changes in both presenilin 1 and 2 genes in the medial temporal lobe cortex following 10-min global brain ischemia in rats. METHODS Global brain ischemia was induced by cardiac arrest in female rats that were allowed to survive for 2, 7 and 30 days. The expression of presenilin genes was evaluated in the rat medial temporal lobe cortex with the use of quantitative RT-PCR analysis. RESULTS Presenilin 1 gene expression tended to be downregulated from days 2 to 7 postischemia but at day 30, there was a reverse tendency. The greatest overexpression of presenilin 2 gene was noted at 2-nd day whilst on day 7, the expression of this gene was only modestly elevated. Eventually, at day 30 expression of presenilin 2 gene was modestly downregulated. Alterations of presenilin 2 gene expression between 2 and 7 days and between 2 and 30 days were statistically significant. CONCLUSIONS Thus, presented changes suggest that the significant dysregulation of presenilin 2 gene may be connected with a response of neuronal cells to transient global brain ischemia due to cardiac arrest. Finally, the ischemia-induced gene dysregulation may play a key role in the late onset of Alzheimers-type dementia.
Pharmacological Reports | 2016
Marzena Ułamek-Kozioł; Ryszard Pluta; Anna Bogucka-Kocka; Sławomir Januszewski; Janusz Kocki; Stanisław J. Czuczwar
There are evidences for the influence of Alzheimers proteins on postischemic brain injury. We present here an overview of the published evidence underpinning the relationships between β-amyloid peptide, hyperphosphorylated tau protein, presenilins, apolipoproteins, secretases and neuronal survival/death decisions after ischemia and development of postischemic dementia. The interactions of above molecules and their influence and contribution to final ischemic brain degeneration resulting in dementia of Alzheimer phenotype are reviewed. Generation and deposition of β-amyloid peptide and tau protein pathology are essential factors involved in Alzheimers disease development as well as in postischemic brain dementia. Postischemic injuries demonstrate that ischemia may stimulate pathological amyloid precursor protein processing by upregulation of β- and γ-secretases and therefore are capable of establishing a vicious cycle. Functional postischemic brain recovery is always delayed and incomplete by an injury-related increase in the amount of the neurotoxic C-terminal of amyloid precursor protein and β-amyloid peptide. Finally, we present here the concept that Alzheimers proteins can contribute to and/or precipitate postischemic brain neurodegeneration including dementia with Alzheimers phenotype.
Journal of Alzheimer's Disease | 2016
Ryszard Pluta; Janusz Kocki; Marzena Ułamek-Kozioł; Alicja Petniak; Paulina Gil-Kulik; Sławomir Januszewski; Jacek Bogucki; Mirosław Jabłoński; Judyta Brzozowska; Wanda Furmaga-Jabłońska; Anna Bogucka-Kocka; Stanisław J. Czuczwar
Brain ischemia may be causally related with Alzheimers disease. Presumably, β-secretase and amyloid-β protein precursor gene expression changes may be associated with Alzheimers disease neuropathology. Consequently, we have examined quantitative changes in both β-secretase and amyloid-β protein precursor genes in the medial temporal lobe cortex with the use of quantitative rtPCR analysis following 10-min global brain ischemia in rats with survival of 2, 7, and 30 days. The greatest significant overexpression of β-secretase gene was noted on the 2nd day, while on days 7-30 the expression of this gene was only modestly downregulated. Amyloid-β protein precursor gene was downregulated on the 2nd day, but on days 7-30 postischemia, there was a significant reverse tendency. Thus, the demonstrated alterations indicate that the considerable changes of expression of β-secretase and amyloid-β protein precursor genes may be connected with a response of neurons in medial temporal lobe cortex to transient global brain ischemia. Finally, the ischemia-induced gene changes may play a key role in a late and slow onset of Alzheimer-type pathology.
Journal of Alzheimer's Disease | 2016
Marzena Ułamek-Kozioł; Janusz Kocki; Anna Bogucka-Kocka; Alicja Petniak; Paulina Gil-Kulik; Sławomir Januszewski; Jacek Bogucki; Mirosław Jabłoński; Wanda Furmaga-Jabłońska; Judyta Brzozowska; Stanisław J. Czuczwar; Ryszard Pluta
Ischemic brain damage is a pathological incident that is often linked with medial temporal lobe cortex injury and finally its atrophy. Post-ischemic brain injury associates with poor prognosis since neurons of selectively vulnerable ischemic brain areas are disappearing by apoptotic program of neuronal death. Autophagy has been considered, after brain ischemia, as a guardian against neurodegeneration. Consequently, we have examined changes in autophagy (BECN 1), mitophagy (BNIP 3), and apoptotic (caspase 3) genes in the medial temporal lobe cortex with the use of quantitative reverse-transcriptase PCR following transient 10-min global brain ischemia in rats with survival 2, 7, and 30 days. The intense significant overexpression of BECN 1 gene was noted on the 2nd day, while on days 7–30 the expression of this gene was still upregulated. BNIP 3 gene was downregulated on the 2nd day, but on days 7–30 post-ischemia, there was a significant reverse tendency. Caspase 3 gene, associated with apoptotic neuronal death, was induced in the same way as BNIP 3 gene after brain ischemia. Thus, the demonstrated changes indicate that the considerable dysregulation of expression of BECN 1, BNIP 3, and caspase 3 genes may be connected with a response of neuronal cells in medial temporal lobe cortex to transient complete brain ischemia.
Pharmacological Reports | 2018
Ryszard Pluta; Anna Bogucka-Kocka; Marzena Ułamek-Kozioł; Jacek Bogucki; Sławomir Januszewski; Janusz Kocki; Stanisław J. Czuczwar
BACKGROUND Tauopathies are a class of neurodegenerative illnesses associated with the aberrant accumulation of the tau protein in the brain. The best known out of these diseases is Alzheimers disease, a disorder where the microtubule associated tau protein becomes hyperphosphorylated (which lowers its binding affinity to microtubules) and accumulates inside neurons in the form of tangles. In this study, we attempt to find out whether brain ischemia may play an important role in tau protein gene alterations. METHODS We have investigated the relationship between hippocampal ischemia and Alzheimers disease by means of a transient 10-min global brain ischemia in rats and determining the effect on Alzheimers disease tau protein gene expression during 2, 7 and 30 days post injury. RESULTS We found the significant overexpression of tau protein gene on the 2nd day, but on days 7 and 30 post-ischemia there a significant opposite tendency was observed. CONCLUSION The obtained results offer a novel insight into tau protein gene in regulating delayed neuronal death in the ischemic hippocampus. Finally, these findings further elucidate the long-term impact of brain ischemia on Alzheimers disease development.BACKGROUND Tauopathies are a class of neurodegenerative illnesses associated with the aberrant accumulation of the tau protein in the brain. The best known out of these diseases is Alzheimers disease, a disorder where the microtubule associated tau protein becomes hyperphosphorylated (which lowers its binding affinity to microtubules) and accumulates inside neurons in the form of tangles. In this study, we attempt to find out whether brain ischemia may play an important role in tau protein gene alterations. METHODS We have investigated the relationship between hippocampal ischemia and Alzheimers disease by means of a transient 10-min global brain ischemia in rats and determining the effect on Alzheimers disease tau protein gene expression during 2, 7 and 30 days post injury. RESULTS We found the significant overexpression of tau protein gene on the 2nd day, but on days 7 and 30 post-ischemia there a significant opposite tendency was observed. CONCLUSION The obtained results offer a novel insight into tau protein gene in regulating delayed neuronal death in the ischemic hippocampus. Finally, these findings further elucidate the long-term impact of brain ischemia on Alzheimers disease development.
Pharmacological Reports | 2017
Marzena Ułamek-Kozioł; Janusz Kocki; Anna Bogucka-Kocka; Sławomir Januszewski; Jacek Bogucki; Stanisław J. Czuczwar; Ryszard Pluta
BACKGROUND Postichemic brain injury correlates with poor prognosis since selectively vulnerable parts of brain are associated with apoptotic neuronal death. But autophagy has been recognized, as a probable survival mechanism following brain ischemia. METHODS We have analyzed, by quantitative reverse-transcriptase PCR assay protocol, three genes: autophagy, mitophagy and caspase 3 for neuronal death response in ischemic hippocampal CA1 area. RESULTS We have found that autophagy gene was not significantly modified at all time points after ischemia, whereas mitophagy and caspase 3 genes were upregulated at day 2 and decreased to basal values at days 7 and 30. CONCLUSION It may be inferred that mitophagy process markedly accompanies apoptosis during delayed neuronal death in hippocampal CA1 area following brain ischemia.