Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(9), С. 5023 - 5023

Опубликована: Апрель 30, 2022

Positron emission tomography (PET) uses radioactive tracers and enables the functional imaging of several metabolic processes, blood flow measurements, regional chemical composition, and/or absorption. Depending on targeted processes within living organism, different are used for various medical conditions, such as cancer, particular brain pathologies, cardiac events, bone lesions, where most commonly radiolabeled with 18F (e.g., [

Язык: Английский

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Nrf2: a dark horse in Alzheimer's disease treatment

Ageing Research Reviews, Год журнала: 2020, Номер 64, С. 101206 - 101206

Опубликована: Ноя. 2, 2020

Язык: Английский

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Synaptic dysfunction in Alzheimer's disease: Mechanisms and therapeutic strategies

Pharmacology & Therapeutics, Год журнала: 2018, Номер 195, С. 186 - 198

Опубликована: Ноя. 12, 2018

Язык: Английский

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Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer’s disease

Journal of Neuroinflammation, Год журнала: 2021, Номер 18(1)

Опубликована: Июнь 11, 2021

Abstract Background Tau pathology is a hallmark of Alzheimer’s disease (AD) and other tauopathies. During progression, abnormally phosphorylated forms tau aggregate accumulate into neurofibrillary tangles, leading to synapse loss, neuroinflammation, neurodegeneration. Thus, targeting expected be promising strategy for AD treatment. Methods The effect rutin on aggregation was detected by thioflavin T fluorescence transmission electron microscope imaging. oligomer-induced cytotoxicity assessed MTT assay. oligomer-mediated the production IL-1β TNF-α in vitro measured ELISA. uptake extracellular microglia determined immunocytochemistry. Six-month-old male Tau-P301S mice were treated with or vehicle oral administration daily 30 days. cognitive performance using Morris water maze test, Y-maze novel object recognition test. levels pathological tau, gliosis, NF-kB activation, proinflammatory cytokines such as TNF-α, synaptic proteins including synaptophysin PSD95 brains evaluated immunolabeling, immunoblotting, Results We showed that rutin, natural flavonoid glycoside, inhibited cytotoxicity, lowered cytokines, protected neuronal morphology from toxic oligomers, promoted microglial oligomers vitro. When applied mouse model tauopathy, reduced levels, regulated hyperphosphorylation increasing PP2A level, suppressed gliosis neuroinflammation downregulating pathway, prevented engulfment, rescued loss brains, resulting significant improvement cognition. Conclusion In combination previously reported therapeutic effects Aβ pathology, drug candidate treatment based its combinatorial Aβ.

Язык: Английский

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Flavonoids as Therapeutic Agents in Alzheimer’s and Parkinson’s Diseases: A Systematic Review of Preclinical Evidences

Oxidative Medicine and Cellular Longevity, Год журнала: 2018, Номер 2018(1)

Опубликована: Янв. 1, 2018

Alzheimer’s and Parkinson’s diseases are considered the most common neurodegenerative disorders, representing a major focus of neuroscience research to understanding cellular alterations pathophysiological mechanisms involved. Several natural products, including flavonoids, able cross blood‐brain barrier known for their central nervous system‐related activity. Therefore, studies being conducted with these chemical constituents analyze activities in slowing down progression diseases. The present systematic review summarizes pharmacological effects flavonoids animal models A PRISMA model was utilized this search. following databases: PubMed, Web Science, BIREME, Science Direct. Based on inclusion criteria, 31 articles were selected discussed review. listed revealed that main targets action disease therapy reduction reactive oxygen species amyloid beta‐protein production, while oxidative potential activation neuronal death. Results showed variety is studied can be promising development new drugs treat Moreover, it possible verify there lack translational clinical evidence compounds.

Язык: Английский

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Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Июль 14, 2023

Abstract Alzheimer’s Disease (AD) contributes to most cases of dementia. Its prominent neuropathological features are the extracellular neuritic plaques and intercellular neurofibrillary tangles composed aggregated β-amyloid (Aβ) hyperphosphorylated tau protein, respectively. In past few decades, disease-modifying therapy targeting Aβ has been focus AD drug development. Even though it is encouraging that two these drugs have recently received accelerated US Food Drug Administration approval for treatment, their efficacy or long-term safety controversial. Tau increasing attention as a potential therapeutic target, since evidence indicates pathology more associated with cognitive dysfunction. Moreover, inflammation, especially neuroinflammation, accompanies pathological processes also linked deficits. Accumulating inflammation complex tight interplay pathology. Here, we review recent on interaction between pathology, focusing post-translational modification dissemination, neuroinflammatory responses, including glial cell activation inflammatory signaling pathways. Then, summarize latest clinical trials neuroinflammation. Sustained increased responses in cells neurons pivotal cellular drivers regulators exacerbation which further its worsening by aggravating responses. Unraveling precise mechanisms underlying relationship neuroinflammation will provide new insights into discovery translation targets other tau-related diseases (tauopathies). Targeting multiple pathologies precision strategies be crucial direction developing tauopathies.

Язык: Английский

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Dural lymphatics regulate clearance of extracellular tau from the CNS

Molecular Neurodegeneration, Год журнала: 2019, Номер 14(1)

Опубликована: Фев. 27, 2019

Alzheimer's disease is characterized by two main neuropathological hallmarks: extracellular plaques of amyloid-β (Aβ) protein and intracellular aggregates tau protein. Although normally a soluble monomer that bind microtubules, in it forms insoluble, hyperphosphorylated the cell body. Aside from its role AD, also involved several other neurodegenerative disorders collectively called tauopathies, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), some frontotemporal dementia, argyrophilic grain (AGD). The prion hypothesis suggests after an initial trigger event, misfolded are released into space, where they spread through different brain regions, enter cells, seeding previously normal forms. Thus understanding mechanisms regulating clearance CNS important. discovery true lymphatic system dura potential mediating Aβ pathology prompted us to investigate clearance.To study brain, we conjugated monomeric human with near-infrared dye cypate, injected this labeled parenchyma both wild-type K14-VEGFR3-Ig transgenic mice, which lack functional system. Following injection performed longitudinal imaging using fluorescence molecular tomography (FMT) quantified calculate brain. To complement this, measured periphery measuring plasma groups mice.Our results show significantly higher amount retained brains vs. wild type mice at 48 72 h post-injection subsequent delayed. We found reference tracer serum albumin (HSA) was delayed mice.The dural appears play important tau, since impaired absence lymphatics. Based on our baseline characterization clearance, future studies warranted look interaction between efficiency function.

Язык: Английский

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Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer’s disease

Nature Aging, Год журнала: 2021, Номер 1(12), С. 1175 - 1188

Опубликована: Дек. 6, 2021

Язык: Английский

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Gene-based therapies for neurodegenerative diseases

Nature Neuroscience, Год журнала: 2021, Номер 24(3), С. 297 - 311

Опубликована: Фев. 1, 2021

Язык: Английский

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A Perspective on Nrf2 Signaling Pathway for Neuroinflammation: A Potential Therapeutic Target in Alzheimer's and Parkinson's Diseases

Frontiers in Cellular Neuroscience, Год журнала: 2022, Номер 15

Опубликована: Янв. 21, 2022

Neuroinflammation plays a pivotal role in Alzheimer's disease (AD) and Parkinson's (PD), the leading causes of dementia. These neurological disorders are characterized by accumulation misfolded proteins such as amyloid-ß (Aß), tau protein α-synuclein, contributing to mitochondrial fragmentation, oxidative stress, neuroinflammation. Misfolded activate microglia, which induces neuroinflammation, expression pro-inflammatory cytokines subsequently facilitates synaptic damage neuronal loss. So far, all proposed drugs were based on inhibition aggregation failed clinical trials. Therefore, treatment options dementia still challenging issue. Thus, it is worthwhile study alternative therapeutic strategies. In this context, there increasing data transcription factor NF- E2 p45-related 2 (Nrf2) redox homeostasis anti-inflammatory functions neurodegenerative disorders. Interestingly, Nrf2 signaling pathway has shown upregulation antioxidant genes, microglia-mediated inflammation, improved function diseases, suggesting activation could be novel approach target pathogenesis. The present review will examine correlation between with neuroinflammation AD PD.

Язык: Английский

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