scholarly journals Cell Cycle Inhibition without Disruption of Neurogenesis Is a Strategy for Treatment of Aberrant Cell Cycle Diseases: An Update

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Da-Zhi Liu ◽  
Bradley P. Ander
Keyword(s):  
Cell Cycle ◽  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Deficits ◽  
Neural Progenitor Cells ◽  
Common Mechanism ◽  
Cns Diseases ◽  
Aberrant Cell ◽  
Cell Cycle Reentry ◽  
Cell Cycle Inhibition

Since publishing our earlier report describing a strategy for the treatment of central nervous system (CNS) diseases by inhibiting the cell cycle and without disrupting neurogenesis (Liu et al. 2010), we now update and extend this strategy to applications in the treatment of cancers as well. Here, we put forth the concept of “aberrant cell cycle diseases” to include both cancer and CNS diseases, the two unrelated disease types on the surface, by focusing on a common mechanism in each aberrant cell cycle reentry. In this paper, we also summarize the pharmacological approaches that interfere with classical cell cycle molecules and mitogenic pathways to block the cell cycle of tumor cells (in treatment of cancer) as well as to block the cell cycle of neurons (in treatment of CNS diseases). Since cell cycle inhibition can also block proliferation of neural progenitor cells (NPCs) and thus impair brain neurogenesis leading to cognitive deficits, we propose that future strategies aimed at cell cycle inhibition in treatment of aberrant cell cycle diseases (i.e., cancers or CNS diseases) should be designed with consideration of the important side effects on normal neurogenesis and cognition.

Abstract 2357: Src Kinase Inhibition Blocks Thrombin-induced Brain Injuries without Cognitive Side Effects

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Da-Zhi Liu ◽  
Bradley P Ander ◽  
Ali Izadi ◽  
Ken Van ◽  
Xinhua Zhan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cognitive Deficits ◽  
Neuronal Cell ◽  
Thrombin Injection ◽  
Cell Cycle Reentry ◽  
Cell Cycle Inhibition ◽  
Mature Neurons ◽  
Cognitive Side Effects

Intracerebral hemorrhage (ICH) activates thrombin, a potent mitogen. Thrombin triggers mitosis by modulating several intracellular mitogenic molecules including Src family kinases. These molecules regulate mitogen-activated protein kinases (MAPKs) and cell cycle proteins such as cyclin-dependent kinases (Cdks); and play critical roles in mitogenic signaling pathways and cell cycle progression. Since aberrant cell cycle reentry results in death of mature neurons, cell cycle inhibition appears to be a candidate strategy for the treatment of neurological diseases including ICH. However, this can also block cell cycle (proliferation) of neural progenitor cells (NPCs) and thus impair brain neurogenesis leading to cognitive deficits. We hypothesized that inhibition of cell cycle by blocking mitogenic signaling molecules (i.e., Src family kinase members) blocks cell cycle reentry of mature neurons without injuring NPCs, which will avoid cognitive side effects during cell cycle inhibition treatment for ICH. Our data shows: (1) Thrombin 30U/ml results in apoptosis of mature neurons via neuronal cell cycle reentry in vitro ; (2) PP2 (Src family kinase inhibitor) 0.3 µM attenuates the thrombin-induced neuronal apoptosis via blocking neuronal cell cycle reentry, but does not affect the viability of NPCs at the same doses in vitro ; (3) Intracerebral ventricular thrombin injection (20U, i.c.v.) results in neuron loss in hippocampus and cognitive deficits 5 weeks after thrombin injection in vivo ; (4) PP2 (1mg/kg, i.p.), given immediately after thrombin injection (i.c.v.), blocks the thrombin-induced neuron loss in hippocampus and cognitive deficits, whereas PP2 on its own at the same doses does not affect normal cognition in vivo . These suggest that Src kinase inhibition prevents hippocampal neuron death via blocking neuronal cell cycle reentry after ICH, but does not affect survival of NPCs.

scholarly journals MRI imaging features of HIV-related central nervous system diseases: diagnosis by pattern recognition in daily practice

2021 ◽  
Author(s):  
Mio Sakai ◽  
Masahiro Higashi ◽  
Takuya Fujiwara ◽  
Tomoko Uehira ◽  
Takuma Shirasaka ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Pattern Recognition ◽  
Nervous System ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Opportunistic Infections ◽  
Primary Cns Lymphoma ◽  
Imaging Features ◽  
Cns Diseases ◽  
Inflammatory Syndrome

AbstractWith the advent of antiretroviral therapy (ART), the prognosis of people infected with human immunodeficiency virus (HIV) has improved, and the frequency of HIV-related central nervous system (CNS) diseases has decreased. Nevertheless, mortality from HIV-related CNS diseases, including those associated with ART (e.g., immune reconstitution inflammatory syndrome) remains significant. Magnetic resonance imaging (MRI) can improve the outlook for people with HIV through early diagnosis and prompt treatment. For example, HIV encephalopathy shows a diffuse bilateral pattern, whereas progressive multifocal leukoencephalopathy, HIV-related primary CNS lymphoma, and CNS toxoplasmosis show focal patterns on MRI. Among the other diseases caused by opportunistic infections, CNS cryptococcosis and CNS tuberculosis have extremely poor prognoses unless diagnosed early. Immune reconstitution inflammatory syndrome shows distinct MRI findings from the offending opportunistic infections. Although distinguishing between HIV-related CNS diseases based on imaging alone is difficult, in this review, we discuss how pattern recognition approaches can contribute to their early differentiation.

scholarly journals Maternal Overnutrition Induces Long-Term Cognitive Deficits across Several Generations

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 7 ◽  
Author(s):  
Gitalee Sarker ◽  
Daria Peleg-Raibstein
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Deficits ◽  
Maternal Obesity ◽  
Cognitive Impairments ◽  
Long Term Effects ◽  
Ample Evidence ◽  
Increased Risk ◽  
Maternal Overnutrition

Ample evidence from epidemiological studies has linked maternal obesity with metabolic disorders such as obesity, cardiovascular disease, and diabetes in the next generation. Recently, it was also shown that maternal obesity has long-term effects on the progeny’s central nervous system. However, very little is known regarding how maternal overnutrition may affect, in particular, the cognitive abilities of the offspring. We reported that first-generation offspring exposed to a maternal high-fat diet (MHFD) displayed age-dependent cognitive deficits. These deficits were associated with attenuations of amino acid levels in the medial prefrontal cortex and the hippocampus regions of MHFD offspring. Here, we tested the hypothesis that MHFD in mice may induce long-term cognitive impairments and neurochemical dysfunctions in the second and third generations. We found that MHFD led to cognitive disabilities and an altered response to a noncompetitive receptor antagonist of the N-Methyl-D-aspartic acid (NMDA) receptor in adult MHFD offspring in both second and third generations in a sex-specific manner. Our results suggest that maternal overnutrition leads to an increased risk of developing obesity in subsequent generations as well as to cognitive impairments, affecting learning and memory processes in adulthood. Furthermore, MHFD exposure may facilitate pathological brain aging which is not a consequence of obesity. Our findings shed light on the long-term effects of maternal overnutrition on the development of the central nervous system and the underlying mechanisms which these traits relate to disease predisposition.

scholarly journals Efficient acylation of gastrodin byAspergillus oryzaewhole-cells in non-aqueous media

RSC Advances ◽  
2019 ◽  
Vol 9 (29) ◽  
pp. 16701-16712 ◽  
Author(s):  
Xiaofeng Li ◽  
Maohua Ma ◽  
Xuan Xin ◽  
Yuqian Tang ◽  
Guanglei Zhao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Half Life ◽  
Aqueous Media ◽  
Bioactive Compound ◽  
Therapeutic Effects ◽  
Gastrodia Elata ◽  
Cns Diseases ◽  
Plant Source ◽  
Wide Range

Gastrodin, a bioactive compound extracted from the plant source ofGastrodia elataBlume, has a wide range of therapeutic effects on central nervous system (CNS) diseases, but suffers from poor brain permeability and short half-life in plasma.

scholarly journals Use of Angong Niuhuang in Treating Central Nervous System Diseases and Related Research

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Guo ◽  
Shaohua Yan ◽  
Lipeng Xu ◽  
Gexin Zhu ◽  
Xiaotong Yu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chinese Medicine ◽  
Viral Encephalitis ◽  
Current Knowledge ◽  
Pharmacological Effects ◽  
Nervous System Diseases ◽  
Central Nervous System Diseases ◽  
Cns Diseases ◽  
Related Research

In Chinese medicine-based therapeutics, Angong Niuhuang pill (ANP) is one of the three most effective formulas for febrile diseases, and it is also used to treat other diseases. This paper reviews current knowledge regarding the clinical and pharmacological effects of ANP for treating different central nervous system (CNS) diseases to confirm its validity and efficacy. These diseases are like centric fever, coma, stroke, and viral encephalitis. This review reveals that various diseases could be treated using the same agent, which is one of the most important principles of traditional Chinese medicine (TCM). According to the “Same Treatment for Different Diseases” principle, ANP might be efficacious in other CNS diseases.

scholarly journals Unraveling of Central Nervous System Disease Mechanisms Using CRISPR Genome Manipulation

2018 ◽  
Vol 10 ◽  
pp. 117957351878746 ◽  
Author(s):  
Aino Vesikansa
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Complex Structure ◽  
Regulation Of Gene Expression ◽  
Central Nervous System Disease ◽  
Brain Diseases ◽  
Biological Research ◽  
Cns Diseases ◽  
The Brain

The complex structure and highly variable gene expression profile of the brain makes it among the most challenging fields to study in both basic and translational biological research. Most of the brain diseases are multifactorial and despite the rapidly increasing genomic data, molecular pathways and causal links between genes and central nervous system (CNS) diseases are largely unknown. The advent of an easy and flexible CRISPR-Cas genome editing technology has rapidly revolutionized the field of functional genomics and opened unprecedented possibilities to dissect the mechanisms of CNS disease. CRISPR-Cas allows a plenitude of applications for both gene-focused and genome-wide approaches, ranging from original “gene scissors” making permanent modifications in the genome to the regulation of gene expression and epigenetics. CRISPR technology provides a unique opportunity to establish new cellular and animal models of CNS diseases and holds potential for breakthroughs in the CNS research and drug development.

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