| 1. |
- Bartfai, Tamas, et al.
(författare)
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Alzheimer Drug Trials : Combination of Safe and Efficacious Biologicals to Break the Amyloidosis-Neuroinflammation Vicious Cycle
- 2020
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Ingår i: ASN Neuro. - : SAGE Publications. - 1759-0914. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Late-onset Alzheimer's disease (LOAD) is a long-enduring neurodegenerative disease that progresses for decades before the symptoms of cognitive decline and loss of executive function are measurable. Amyloid deposits among other pathological changes, tau hyperphosphorylation, synapse loss, microglia and astroglia activation, and hippocampal atrophy are among the pathological hallmarks of the disease. These are present in the brain before memory complaints are reported and an AD diagnosis is made. The attempt to postpone or prevent the disease is becoming a more and more plausible goal because new early electrophysiological, cognitive, blood-based, and imaging-based diagnostics are being brought forward at the same time as the first anti-amyloid antibody is about to be approved. In view of known contributions of neuroinflammation to the pathology of LOAD, we should not focus solely on anti-amyloid therapies and ignore the interactive neuroinflammatory component of AD. Our belief is that it would be more rewarding to start clinical trials using combination therapies that are based on approved, safe, and efficacious anti-neuroinflammatory agents such as anti-interleukin-1 signaling agents in combination with the anti-amyloid antibodies that have been shown to be safe in multiyear trials. The proposal is that we should administer these two classes of safe biologicals to symptom-free individuals in midlife who are identified as having a high-risk-for-Alzheimer's-disease using precision medicine.
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| 2. |
- Hetze, S, et al.
(författare)
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Rodent Models to Analyze the Glioma Microenvironment
- 2021
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Ingår i: ASN neuro. - : SAGE Publications. - 1759-0914. ; 13, s. 17590914211005074-
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Tidskriftsartikel (refereegranskat)abstract
- Animal models are still indispensable for understanding the basic principles of glioma development and invasion. Preclinical approaches aim to analyze the treatment efficacy of new drugs before translation into clinical trials is possible. Various animal disease models are available, but not every approach is useful for addressing specific questions. In recent years, it has become increasingly evident that the tumor microenvironment plays a key role in the nature of glioma. In addition to providing an overview, this review evaluates available rodent models in terms of usability for research on the glioma microenvironment.
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| 3. |
- Kawamura, Takuya, et al.
(författare)
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Therapeutic Effect of Nicotinamide Mononucleotide for Hypoxic-Ischemic Brain Injury in Neonatal Mice
- 2023
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Ingår i: Asn Neuro. - 1759-0914. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- A clinical challenge remains in the treatment of hypoxic-ischemic brain injury in newborns. Nicotinamide adenine dinucleotide (NAD+) has beneficial effects in animal models of adult stroke. Here, we aimed to understand the short- and long-term neuroprotective effects of NAD+-promoting substance nicotinamide mononucleotide (NMN) in a well-established brain injury model in neonatal mice. Postnatal day (PND) 9 male and female mice were subjected to cerebral hypoxia-ischemia and treated with saline or NMN (50 mg/kg) immediately after hypoxia-ischemia. At different time points after hypoxia-ischemia, hippocampal NAD+, caspase-3 activity, protein expression of SIRT1, SIRT6, release of high mobility group box-1 (HMGB1), long-term neuropathological outcome, short-term developmental behavior, and long-term motor and memory function were evaluated. Neonatal hypoxia-ischemia reduced NAD+ and SIRT6 levels, but not SIRT1, in the injured hippocampus, while HMGB1 release was significantly increased. NMN treatment normalized hippocampal NAD+ and SIRT6 levels, while caspase-3 activity and HMGB1 release were significantly reduced. NMN alleviated tissue loss in the long-term and improved early developmental behavior, as well as motor and memory function. This study shows that NMN treatment provides neuroprotection in a clinically relevant neonatal animal model of hypoxia-ischemia in mice suggesting as a possible novel treatment for neonatal brain injury.Summary StatementNeonatal hypoxia-ischemia reduces nicotinamide adenine dinucleotide (NAD+) and SIRT6 levels in the injured hippocampus.Hippocampal high mobility group box-1 (HMGB1) release is significantly increased after neonatal hypoxia-ischemia.Nicotinamide mononucleotide (NMN) treatment normalizes hippocampal NAD+ and SIRT6 levels, with significant decrease in caspase-3 activity and HMGB1 release.NMN improves early developmental behavior, as well as motor and memory function. Graphical AbstractThis is a visual representation of the abstract.
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| 4. |
- Zhou, Jiaming, et al.
(författare)
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Pyruvate Kinase 2, an Energy Metabolism Related Enzyme, May Have a Neuroprotective Function in Retinal Degeneration
- 2023
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Ingår i: ASN Neuro. - : SAGE Publications. - 1759-0914. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Retinitis pigmentosa (RP) is an inherited disorder that results in vision impairment but general and mutation-independent therapeutic strategies are not available. However, it is widely regarded that the cGMP system, including cGMP and its interactor cGMP-dependent protein kinase (PKG), acts as a crucial effector during retinal degeneration. We have previously identified a list of cGMP-PKG-dependent genes in the context of RP, and in this study, we further validated one of these, namely pyruvate kinase 2 (PKM2), and investigated the potential role of PKM2 for the photoreceptors’ well-being during RP. With the aid of organotypic retinal explant cultures, we pharmacologically manipulated the PKM2 activities in two different RP mouse models (rd2 and rd10) via the addition of TEPP-46 (a PKM2 activator) and found that activation of PKM2 alleviates the progress of photoreceptor death in the rd10 mouse model. We also noted that the expression of both PKM2 and one of its targets, glucose transporter-1 (Glut1), showed alterations depending on the degeneration state. The observations provide supportive evidence that PKM2 may serve as a novel potential molecular target in RP.
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