A new tau dephosphorylation-targeting chimera for the treatment of tauopathies.

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

Ankylosing spondylitis coexisting with Clonorchis sinensis infection: A case report.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease. The prevailing theory links AS onset to infections in susceptible individuals. Furthermore, infections may impair the immune responses. Numerous studies have investigated links between AS and various infections-bacterial, viral, fungal, and other microorganism infections. However, limited attention has been given to the association between AS and Clonorchis sinensis (C. sinensis) infection. CASE SUMMARY: A 27-year-old male with a 10-yr history of AS presented to our hospital with inflammatory lower back pain as the primary manifestation. Ten years ago, the patient had achieved a stable condition after treatment with biological agents. However, he experienced a recurrence of lumbosacral pain with an unexplained cause 10 d before hospital admission. A lumbosacral magnetic resonance imaging (MRI) scan revealed bone marrow edema in the left sacroiliac joint, and laboratory indicators were elevated. Moreover, the presence of C. sinensis eggs was detected in the stool. The patient was prescribed praziquantel, resulting in the disappearance of C. sinensis eggs in subsequent routine stool tests and relief from lumbosacral pain. A follow-up MRI scan performed after 4 months revealed a reduction in bone marrow edema around the left sacroiliac joint. CONCLUSION: C. sinensis infections could potentially trigger the exacerbation of AS. Clinicians should pay attention to investigating the presence of infections.

Exercised-enriched blood plasma rescues hippocampal impairments and cognitive deficits in an Alzheimer's disease model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and moderate exercise holds promise in ameliorating the ongoing neurodegeneration and cognitive decline. Here, we investigated whether exercise-enriched blood plasm could yield a beneficial therapeutic effect on AD pathologies and cognitive decline in transgenic AD (P301S) mice. In this investigation, a cohort of 2-month-old C57BL/6 mice were granted continuous access to either a running wheel or a fixed wheel for 6 weeks. After that, their plasmas were extracted and subsequently injected intravenously into 4.5-month-old P301S mice biweekly over a 6-week period. A comprehensive methodology was then employed, integrating behavioral tests, pathology assessments, and biochemical analyses to unveil the potential anti-dementia implications of exercise-enriched blood plasma in P301S mice. Upon systemic administration, the findings revealed a noteworthy attenuation of hippocampus-dependent behavioral impairments in P301S mice. Conversely, blood plasma from sedentary counterparts exhibited no discernible impact. These effects were intricately associated with the mitigation of neuroinflammation, the augmentation of hippocampal adult neurogenesis, and a reduction of synaptic impairments following the administration of exercise-enriched blood plasma. These findings advance the proposition that administering exercise-enriched blood plasma may serve as an effective prophylactic measure against AD, opening avenues for further exploration and potential therapeutic interventions.

ω-3PUFAs Prevent MK-801-induced Cognitive Impairment in Schizophrenic Rats via the CREB/BDNF/TrkB Pathway / 华中科技大学学报（医学）（英德文版）

This study was to determine the protective effect of ω-3 polyunsaturated fatty acids (ω-3PUFAs) on MK-801-induced cognitive impairment in schizophrenia (SZ) rats and the underlying mechanism.A rat model of schizophrenia was induced by MK-801.The cognitive function of rats was assessed using a Morris water maze.The number of hippocampal neurons was measured by Nissl staining.The expression of CREB,p-CREB,BDNF,TrkB,p-TrkB,AKT,p-AKT,ERK,and p-ERK in the hippocampus of rats was detected by Western blotting.The results showed that ω-3PUFAs attenuated MK-801-induced cognitive,impairment and hippocampal neurons loss,reversed the injury of the CREB/BDNF/TrtB pathway induced by MK-801,and antagonized MK-801-induced down-regulation of p-AKT and p-ERK in the hippocampus of rats.In conclusion,ω-3PUFAs enhances the CREB/BDNF/TrkB pathway by activating ERK and AKT,thereby increasing the synaptic plasticity and decreashng neuron loss,and antagonizing MK-801-induced cognitive impairment in schizophrenic rats.

Long-term Helicobacter pylori Infection Does Not Induce Tauopathy and Memory Impairment in SD Rats / 华中科技大学学报（医学）（英德文版）

Helicobacter pylori (H.pylori) infection is a recognized risk factor of dementia,while its role and mechanism in Alzheimer disease (AD) remained unclarified.Our previous study has identified that injection of soluble H.pylori filtrate could induce AD-like pathologic changes and cognitive impairment in SD rats.In the present study,we further explored the effect of long-term stomach colonization of H.pylori bacteria on the brains of SD rats.The results showed that H.pylori bacteria gavage induced an efficient colonization of H.pylori in the stomach after four weeks.However,there was no significant change of tau phosphorylation at Thr205 (pT205),Thr231 (pT231),Ser396 (pS396) and Ser404 (pS404) sites in the hippocampus and cerebral cortex.The H.pylori-infected rats also showed no cognitive impairment.These observations may result from inefficient release of bacterial pathogenic factors or the overall lack of host inflammatory responses.We conclude that SD rat with long-term H.pylori colonization in the stomach is not a suitable animal model for exploring the effects of H.pylori infection on brain function in human beings;administration of bacterial filtrates may better reveal the systemic pathologic changes induced by bacterial infection in animals which show a negative host response to bacterial colonization.