ArticleBritish journal of pharmacology2022
Control of hippocampal prothrombin kringle-2 (pKr-2) expression reduces neurotoxic symptoms in five familial Alzheimer's disease mice.
Article in British journal of pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Therapeutic targeting of blood-derived protein infiltration to modulate neuroinflammation in cerebellar ataxia.Journal of neuroinflammation · 2026Article
- Nanotechnology to Overcome Blood-Brain Barrier Permeability and Damage in Neurodegenerative Diseases.Pharmaceutics · 2025Review
- The Crucial Role of the Blood-Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications.Journal of clinical medicine · 2025Review
- Role of Oxidative Stress in Blood-Brain Barrier Disruption and Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Thinking outside the black box: are the brain endothelial cells the new main target in Alzheimer's disease?Neural regeneration research · 2023Review
- Pathophysiological Role of Microglial Activation Induced by Blood-Borne Proteins in Alzheimer's Disease.Biomedicines · 2023Review
- pKr-2 induces neurodegenerationBrain, behavior, & immunity - health · 2023Article
- Potential roles of the endoplasmic reticulum stress pathway in amyotrophic lateral sclerosis.Frontiers in aging neuroscience · 2023Review
- Prothrombin kringle-2, a mediator of microglial activation: new insight in Alzheimer's disease pathogenesis.Neural regeneration research · 2022Article
- Addressing Blood-Brain Barrier Impairment in Alzheimer's Disease.Biomedicines · 2022Review
- Control of hippocampal prothrombin kringle-2 (pKr-2) expression reduces neurotoxic symptoms in five familial Alzheimer's disease mice.British journal of pharmacology · 2022Article
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Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThere is a scarcity of information regarding the role of prothrombin kringle-2 (pKr-2), which can be generated by active thrombin, in hippocampal neurodegeneration and Alzheimer's disease (AD). EXPERIMENTAL APPROACH: To assess the role of pKr-2 in association with the neurotoxic symptoms of AD, we determined pKr-2 protein levels in post-mortem hippocampal tissues of patients with AD and the hippocampi of five familial AD (5XFAD) mice compared with those of age-matched controls and wild-type (WT) mice, respectively. In addition, we investigated whether the hippocampal neurodegeneration and object memory impairments shown in 5XFAD mice were mediated by changes to pKr-2 up-regulation. KEY
resultsOur results demonstrated that pKr-2 was up-regulated in the hippocampi of patients with AD and 5XFAD mice, but was not associated with amyloid-β aggregation in 5XFAD mice. The up-regulation of pKr-2 expression was inhibited by preservation of the blood-brain barrier (BBB) via addition of caffeine to their water supply or by treatment with rivaroxaban, an inhibitor of factor Xa that is associated with thrombin production. Moreover, the prevention of up-regulation of pKr-2 expression reduced neurotoxic symptoms, such as hippocampal neurodegeneration and object recognition decline due to neurotoxic inflammatory responses in 5XFAD mice. CONCLUSION AND IMPLICATIONS: We identified a novel pathological mechanism of AD mediated by abnormal accumulation of pKr-2, which functions as an important pathogenic factor in the adult brain via blood brain barrier (BBB) breakdown. Thus, pKr-2 represents a novel target for AD therapeutic strategies and those for related conditions.
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