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

Pluta, Ryszard; Czuczwar, Stanisław J.; Januszewski, Sławomir; Jabłoński, Mirosław

doi:10.3390/cells10092213

Cited by 16 publications

(37 citation statements)

References 153 publications

(298 reference statements)

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“…It is interesting to note that BBB disruption can lead to different neurological disorders, depending on the inflammatory molecules and pathological proteins present in the milieu. For example, BBB disruption allows tau proteins to enter the brain which has been implicated in the pathology of Alzheimer’s disease [ 79 , 80 ]. On the other hand, enhanced BBB permeability leads to the entry of inflammatory molecules (such as TNF-α) and free radicals such as nitric oxide which may determine predisposition to ASD [ 81 ].…”

Section: Discussionmentioning

confidence: 99%

Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model

Memis

Mittal

Furar

et al. 2022

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core symptoms, specifically impaired social behavior, stereotypic/repetitive behaviors, and sensory/communication deficits. Although the exact pathophysiology of ASD is still unknown, host genetics, oxidative stress, and compromised blood brain barrier (BBB) have been implicated in predisposition to ASD. With regards to genetics, mutations in the genes such as CNTNAP2 have been associated with increased susceptibility of developing ASD. Although some studies observed conflicting results suggesting no association of CNTNAP2 with ASD, other investigations correlated this gene with autism. In addition, CNTNAP2 mediated signaling is generally considered to play a role in neurological disorders due to its critical role in neurodevelopment, neurotransmission, and synaptic plasticity. In this investigation, we studied BBB integrity and oxidative stress in Cntnap2−/− rats. We observed that the BBB permeability was significantly increased in Cntnap2−/− rats compared to littermate wild-type (WT) animals as determined by FITC-dextran and Evans blue assay. High levels of thiobarbituric acid reactive substances and lower amounts of reduced glutathione were observed in brain homogenates of Cntnap2−/− rats, suggesting oxidative stress. Brain sections from Cntnap2−/− rats showed intense inducible nitric oxide synthase immunostaining, which was undetectable in WT animals. Quantification of nitric oxide in brain homogenates revealed significantly high levels in Cntnap2−/− rats compared to the control group. As increased permeability of the BBB and oxidative stress have been observed in ASD individuals, our results suggest that Cntnap2−/− rats have a high construct and face validity and can be explored to develop effective therapeutic modalities.

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Section: Discussionmentioning

confidence: 99%

Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model

Memis

Mittal

Furar

et al. 2022

JCM

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“…Hyperphosphorylated tau protein, among other things, triggers oxidative stress, causes mitochondrial dysfunction, and ultimately contributes to the progressive development of brain neurodegeneration [116]. The hyperphosphorylation and accumulation of tau protein in the form of neurofibrillary tangles are regulated by several tau protein kinases, the most common of them being glycogen synthase kinase-3β and the mitogen-activated protein kinase [39,54,96,117]. Common tau protein kinases that pathologically phosphorylate the tau protein are extracellular signal-regulated kinase 2, cyclin-dependent kinase 5, S6 kinase, SAD kinase, microtubule affinity regulating kinase, protein kinase A, calcium/calmodulin II dependent protein kinase, and kinases Fyn and c-Abl.…”

Section: Curcumin and Tau Proteinmentioning

confidence: 99%

“…Third, evidence shows that cerebral ischemia in animals and humans induces the production and accumulation of amyloid in the form of amyloid plaques [26,[29][30][31][32][33][34]. Fourth, research indicates that hyperphosphorylation of the tau protein with the final formation of neurofibrillary tangles also plays a key role in the development of post-ischemic brain neurodegeneration as in Alzheimer's disease [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. Fifth, dysfunction of the autophagy, mitophagy, and apoptosis genes is involved in post-ischemic neurodegeneration, as in Alzheimer's disease [55][56][57].…”

Section: Introductionmentioning

confidence: 99%

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Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Possible Therapeutic Role of Curcumin

et al. 2022

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For thousands of years, mankind has been using plant extracts or plants themselves as medicinal herbs. Currently, there is a great deal of public interest in naturally occurring medicinal substances that are virtually non-toxic, readily available, and have an impact on well-being and health. It has been noted that dietary curcumin is one of the regulators that may positively influence changes in the brain after ischemia. Curcumin is a natural polyphenolic compound with pleiotropic biological properties. The observed death of pyramidal neurons in the CA1 region of the hippocampus and its atrophy are considered to be typical changes for post-ischemic brain neurodegeneration and for Alzheimer’s disease. Additionally, it has been shown that one of the potential mechanisms of severe neuronal death is the accumulation of neurotoxic amyloid and dysfunctional tau protein after cerebral ischemia. Post-ischemic studies of human and animal brains have shown the presence of amyloid plaques and neurofibrillary tangles. The significant therapeutic feature of curcumin is that it can affect the aging-related cellular proteins, i.e., amyloid and tau protein, preventing their aggregation and insolubility after ischemia. Curcumin also decreases the neurotoxicity of amyloid and tau protein by affecting their structure. Studies in animal models of cerebral ischemia have shown that curcumin reduces infarct volume, brain edema, blood-brain barrier permeability, apoptosis, neuroinflammation, glutamate neurotoxicity, inhibits autophagy and oxidative stress, and improves neurological and behavioral deficits. The available data suggest that curcumin may be a new therapeutic substance in both regenerative medicine and the treatment of neurodegenerative disorders such as post-ischemic neurodegeneration.

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“…Multiple studies imply that cholinergic synaptic transmission plays a key role in enhancing cognitive performance, brain functioning, and plasticity. As a result, subsequent research is oriented toward investigating the normal cognitive abilities and age-associated cognitive impairments caused due to the brain’s cholinergic system ( Kaur et al, 2021 ; Pluta et al, 2021 ). The cholinergic theory transformed Alzheimer’s investigational studies from an observational and explanatory neuropathological study to the present paradigm of synaptic neurotransmission.…”

Section: The Cholinergic Hypothesismentioning

confidence: 99%

Natural Therapeutics in Aid of Treating Alzheimer’s Disease: A Green Gateway Toward Ending Quest for Treating Neurological Disorders

et al. 2022

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The current scientific community is facing a daunting challenge to unravel reliable natural compounds with realistic potential to treat neurological disorders such as Alzheimer’s disease (AD). The reported compounds/drugs mostly synthetic deemed the reliability and therapeutic potential largely due to their complexity and off-target issues. The natural products from nutraceutical compounds emerge as viable preventive therapeutics to fill the huge gap in treating neurological disorders. Considering that Alzheimer’s disease is a multifactorial disease, natural compounds offer the advantage of a multitarget approach, tagging different molecular sites in the human brain, as compared with the single-target activity of most of the drugs so far used to treat Alzheimer’s disease. A wide range of plant extracts and phytochemicals reported to possess the therapeutic potential to Alzheimer’s disease includes curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, oleocanthal, and other phytochemicals such as huperzine A, limonoids, and azaphilones. Reported targets of these natural compounds include inhibition of acetylcholinesterase, amyloid senile plaques, oxidation products, inflammatory pathways, specific brain receptors, etc. We tenaciously aimed to review the in-depth potential of natural products and their therapeutic applications against Alzheimer’s disease, with a special focus on a diversity of medicinal plants and phytocompounds and their mechanism of action against Alzheimer’s disease pathologies. We strongly believe that the medicinal plants and phytoconstituents alone or in combination with other compounds would be effective treatments against Alzheimer’s disease with lesser side effects as compared to currently available treatments.

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

Cited by 16 publications

References 153 publications

Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model

Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model

Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Possible Therapeutic Role of Curcumin

Natural Therapeutics in Aid of Treating Alzheimer’s Disease: A Green Gateway Toward Ending Quest for Treating Neurological Disorders

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