Participation of Amyloid and Tau Protein in Post-Ischemic Neurodegeneration of the Hippocampus of a Nature Identical to Alzheimer's Disease

Pluta, Ryszard; Ouyang, Liang; Januszewski, Sławomir; Li, Yang; Czuczwar, Stanisław J.

doi:10.3390/ijms22052460

Cited by 28 publications

(40 citation statements)

References 133 publications

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“…1A). Given that p-Tau217 is an early marker of neurodegeneration and Alzheimer's [20,27,28], these results are consistent with the role of phosphorylated Tau in HAND pathogenesis and suggest that increase in this factor may precede HAND diagnosis. Amyloidogenic proteins and amyloid peptides are associated with lipid rafts [29][30][31][32][33], and our previous study suggested that increased abundance of lipid rafts caused by Nef-containing extracellular vesicles (exNef) may be the reason for the upregulation of APP and Tau [11].…”

Section: Resultssupporting

confidence: 70%

Section: Resultssupporting

confidence: 70%

“…The copyright holder for this preprint (which this version posted July 21, 2021. ; https://doi.org/10.1101/2021.07.20.453134 doi: bioRxiv preprint diagnosis, and 12 uninfected controls without diagnosed neurological disease (Table S1) for Tau protein phosphorylated on Threonine 217 (p-Tau217). This Tau isoform has been shown to strongly correlate with Aβ deposition [26] and was proposed as a marker for Alzheimer's disease [20,27,28]. Results presented in Fig.…”

Section: Resultsmentioning

confidence: 92%

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Abundance of Nef and p-Tau217 in brains of individuals diagnosed with HIV-associated neurocognitive disorders correlate with disease severance

Pushkarsky

Ward

Sviridov

et al. 2021

Preprint

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HIV-associated neurological disorders (HAND) is a term used to describe a variety of neurological impairments observed in HIV-infected individuals. The pathogenic mechanisms of HAND and of its connection to HIV infection remain unknown. Previous studies suggested that HIV-1 Nef may contribute to HAND by impairing cholesterol metabolism, increasing abundance of lipid rafts and affecting their functionality. Our comparative analysis of post-mortem brain samples demonstrated a trend towards decreased abundance of cholesterol transporter ABCA1 in samples from HIV-infected ART-treated individuals relative to samples from uninfected controls, and a reverse correlation between ABCA1 and flotillin 1, a marker for lipid rafts, in all analyzed samples. The brain samples from HIV-infected individuals, both with and without HAND, were characterized by increased abundance of p-Tau217 peptide, which correlated with the abundance of flotillin 1. HIV-1 Nef was detected in some, but not all, samples from HAND-affected individuals. Samples positive for Nef had lower abundance of ABCA1, higher abundance of flotillin 1 and p-Tau217, and were obtained from individuals with higher severity of HAND relative to Nef-negative samples. These results highlight the contribution of Nef and Nef-dependent impairment of cholesterol metabolism to the pathogenesis of HAND and support a connection between pathogenesis of HAND and Alzheimer disease.

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Section: Resultssupporting

confidence: 70%

Section: Resultssupporting

confidence: 70%

Section: Resultsmentioning

confidence: 92%

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Abundance of Nef and p-Tau217 in brains of individuals diagnosed with HIV-associated neurocognitive disorders correlate with disease severance

Pushkarsky

Ward

Sviridov

et al. 2021

Preprint

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“…The above observations show that the tau protein may be at the intersection of many pathological mechanisms/processes/phenomena leading to severe neurodegenerative changes in the brain after ischemia. The facts show that an ischemic brain injury induces neuronal damage and death in the hippocampus via a tau protein-dependent mechanism, defining a new phenomenon that influences the long-term survival and/or death of post-ischemic neurons ( Table 2 , Figure 1 ) [ 33 , 34 , 41 , 42 , 49 , 60 , 63 , 64 , 67 , 68 , 149 , 150 , 151 ]. The underlying processes of neuronal death following ischemia include neuropathological effects in the tau protein.…”

Section: Discussionmentioning

confidence: 99%

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

Pluta

Czuczwar

Januszewski

et al. 2021

Cells

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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.

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“…There is extensive evidence pointing to a close relationship between brain ischemia and AD [ 66 , 184 ]. Amyloid hypothesis assumes aberrant upregulation of Aβ production and/or its reduced clearance, which results in its accumulation in the brain.…”

Section: Discussionmentioning

confidence: 99%

Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

Miziak

Błaszczyk²,

Czuczwar

2021

Pharmaceuticals

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Alzheimer’s disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. The PUBMED, Medical Subject Heading and Clinical Trials databases were used for searching relevant data. Novel treatments are focused on already approved drugs for other conditions and also searching for innovative drugs encompassing investigational compounds. Among the approved drugs, we investigated, are intranasal insulin (and other antidiabetic drugs: liraglitude, pioglitazone and metformin), bexarotene (an anti-cancer drug and a retinoid X receptor agonist) or antidepressant drugs (citalopram, escitalopram, sertraline, mirtazapine). The latter, especially when combined with antipsychotics (for instance quetiapine or risperidone), were shown to reduce neuropsychiatric symptoms in AD patients. The former enhanced cognition. Procognitive effects may be also expected with dietary antioxidative and anti-inflammatory supplements—curcumin, myricetin, and resveratrol. Considering a close relationship between brain ischemia and AD, they may also reduce post-brain ischemia neurodegeneration. An investigational compound, CN-105 (a lipoprotein E agonist), has a very good profile in AD preclinical studies, and its clinical trial for postoperative dementia is starting soon.

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Participation of Amyloid and Tau Protein in Post-Ischemic Neurodegeneration of the Hippocampus of a Nature Identical to Alzheimer's Disease

Cited by 28 publications

References 133 publications

Abundance of Nef and p-Tau217 in brains of individuals diagnosed with HIV-associated neurocognitive disorders correlate with disease severance

Abundance of Nef and p-Tau217 in brains of individuals diagnosed with HIV-associated neurocognitive disorders correlate with disease severance

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

Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

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