scholarly journals Enzyme Replacement Improves Ataxic Gait and Central Nervous System Histopathology in a Mouse Model of Metachromatic Leukodystrophy

2009 ◽  
Vol 17 (4) ◽  
pp. 600-606 ◽  
Author(s):  
Ulrich Matzner ◽  
Renate Lüllmann-Rauch ◽  
Stijn Stroobants ◽  
Claes Andersson ◽  
Cecilia Weigelt ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Metachromatic Leukodystrophy ◽  
Ataxic Gait ◽  
Enzyme Replacement

scholarly journals Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy

2005 ◽  
Vol 14 (9) ◽  
pp. 1139-1152 ◽  
Author(s):  
Ulrich Matzner ◽  
Eva Herbst ◽  
Kerstin Khalaj Hedayati ◽  
Renate Lüllmann-Rauch ◽  
Carsten Wessig ◽  
...  
Keyword(s):  
Nervous System ◽  
Mouse Model ◽  
Metachromatic Leukodystrophy ◽  
Enzyme Replacement ◽  
And Function

New Advanced Strategies for the Treatment of Lysosomal Diseases Affecting the Central Nervous System

2019 ◽  
Vol 25 (17) ◽  
pp. 1933-1950 ◽  
Author(s):  
Maria R. Gigliobianco ◽  
Piera Di Martino ◽  
Siyuan Deng ◽  
Cristina Casadidio ◽  
Roberta Censi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Polymeric Nanoparticles ◽  
Genetic Diseases ◽  
Point Of View ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Lysosomal Diseases ◽  
The Central Nervous System ◽  
Enzyme Delivery

Lysosomal Storage Disorders (LSDs), also known as lysosomal diseases (LDs) are a group of serious genetic diseases characterized by not only the accumulation of non-catabolized compounds in the lysosomes due to the deficiency of specific enzymes which usually eliminate these compounds, but also by trafficking, calcium changes and acidification. LDs mainly affect the central nervous system (CNS), which is difficult to reach for drugs and biological molecules due to the presence of the blood-brain barrier (BBB). While some therapies have proven highly effective in treating peripheral disorders in LD patients, they fail to overcome the BBB. Researchers have developed many strategies to circumvent this problem, for example, by creating carriers for enzyme delivery, which improve the enzyme’s half-life and the overexpression of receptors and transporters in the luminal or abluminal membranes of the BBB. This review aims to successfully examine the strategies developed during the last decade for the treatment of LDs, which mainly affect the CNS. Among the LD treatments, enzyme-replacement therapy (ERT) and gene therapy have proven effective, while nanoparticle, fusion protein, and small molecule-based therapies seem to offer considerable promise to treat the CNS pathology. This work also analyzed the challenges of the study to design new drug delivery systems for the effective treatment of LDs. Polymeric nanoparticles and liposomes are explored from their technological point of view and for the most relevant preclinical studies showing that they are excellent choices to protect active molecules and transport them through the BBB to target specific brain substrates for the treatment of LDs.

scholarly journals The Function of Selenium in Central Nervous System: Lessons from MsrB1 Knockout Mouse Models

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1372
Author(s):  
Tengrui Shi ◽  
Jianxi Song ◽  
Guanying You ◽  
Yujie Yang ◽  
Qiong Liu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Knockout Mouse Model ◽  
The Central Nervous System

MsrB1 used to be named selenoprotein R, for it was first identified as a selenocysteine containing protein by searching for the selenocysteine insert sequence (SECIS) in the human genome. Later, it was found that MsrB1 is homologous to PilB in Neisseria gonorrhoeae, which is a methionine sulfoxide reductase (Msr), specifically reducing L-methionine sulfoxide (L-Met-O) in proteins. In humans and mice, four members constitute the Msr family, which are MsrA, MsrB1, MsrB2, and MsrB3. MsrA can reduce free or protein-containing L-Met-O (S), whereas MsrBs can only function on the L-Met-O (R) epimer in proteins. Though there are isomerases existent that could transfer L-Met-O (S) to L-Met-O (R) and vice-versa, the loss of Msr individually results in different phenotypes in mice models. These observations indicate that the function of one Msr cannot be totally complemented by another. Among the mammalian Msrs, MsrB1 is the only selenocysteine-containing protein, and we recently found that loss of MsrB1 perturbs the synaptic plasticity in mice, along with the astrogliosis in their brains. In this review, we summarized the effects resulting from Msr deficiency and the bioactivity of selenium in the central nervous system, especially those that we learned from the MsrB1 knockout mouse model. We hope it will be helpful in better understanding how the trace element selenium participates in the reduction of L-Met-O and becomes involved in neurobiology.

scholarly journals Microglia control small vessel calcification via TREM2

2021 ◽  
Vol 7 (9) ◽  
pp. eabc4898
Author(s):  
Yvette Zarb ◽  
Sucheta Sridhar ◽  
Sina Nassiri ◽  
Sebastian Guido Utz ◽  
Johanna Schaffenrath ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Vascular Calcification ◽  
Neurovascular Unit ◽  
Small Vessel ◽  
Vascular Pathology ◽  
Cns Development ◽  
Brain Calcification

Microglia participate in central nervous system (CNS) development and homeostasis and are often implicated in modulating disease processes. However, less is known about the role of microglia in the biology of the neurovascular unit (NVU). In particular, data are scant on whether microglia are involved in CNS vascular pathology. In this study, we use a mouse model of primary familial brain calcification, Pdgfbret/ret, to investigate the role of microglia in calcification of the NVU. We report that microglia enclosing vessel calcifications, coined calcification-associated microglia, display a distinct activation phenotype. Pharmacological ablation of microglia with the CSF1R inhibitor PLX5622 leads to aggravated vessel calcification. Mechanistically, we show that microglia require functional TREM2 for controlling vascular calcification. Our results demonstrate that microglial activity in the setting of pathological vascular calcification is beneficial. In addition, we identify a previously unrecognized function of microglia in halting the expansion of vascular calcification.

scholarly journals A neonatal mouse model of central nervous system infections caused by Coxsackievirus B5

2018 ◽  
Vol 7 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Qunying Mao ◽  
Xiaotian Hao ◽  
Yalin Hu ◽  
Ruixiao Du ◽  
Shuhui Lang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Neonatal Mouse ◽  
Central Nervous System Infections

scholarly journals Morbillivirus Infection of the Mouse Central Nervous System Induces Region-Specific Upregulation of MMPs and TIMPs Correlated to Inflammatory Cytokine Expression

2001 ◽  
Vol 75 (17) ◽  
pp. 8268-8282 ◽  
Author(s):  
Seng-Thuon Khuth ◽  
Hideo Akaoka ◽  
Axel Pagenstecher ◽  
Olivier Verlaeten ◽  
Marie-Françoise Belin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Neurological Disorders ◽  
Dynamic Balance ◽  
Brain Structures ◽  
Cytokine Expression ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Cns Infection ◽  
Necrosis Factor Alpha

ABSTRACT Viral infection of the central nervous system (CNS) can result in perturbation of cell-to-cell communication involving the extracellular matrix (ECM). ECM integrity is maintained by a dynamic balance between the synthesis and proteolysis of its components, mainly as a result of the action of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). An MMP/TIMP imbalance may be critical in triggering neurological disorders, in particular in virally induced neural disorders. In the present study, a mouse model of brain infection using a neurotropic strain of canine distemper virus (CDV) was used to study the effect of CNS infection on the MMP/TIMP balance and cytokine expression. CDV replicates almost exclusively in neurons and has a unique pattern of expression (cortex, hypothalamus, monoaminergic nuclei, hippocampus, and spinal cord). Here we show that although several mouse brain structures were infected, they exhibited a differential pattern in terms of MMP, TIMP, and cytokine expression, exemplified by (i) a large increase in pro-MMP9 levels, in particular in the hippocampus, which occurred mainly in neurons and was associated with in situ gelatinolytic activity, (ii) specific and significant upregulation of MT1-MMP mRNA expression in the cortex and hypothalamus, (iii) an MMP/TIMP imbalance, suggested by the upregulation of TIMP-1 mRNA in the cortex, hippocampus, and hypothalamus and of TIMP-3 mRNA in the cortex, and (iv) a concomitant region-specific large increase in expression of Th1-like cytokines, such as gamma interferon, tumor necrosis factor alpha, and interleukin 6 (IL-6), contrasting with weaker induction of Th2-like cytokines, such as IL-4 and IL-10. These data indicate that an MMP/TIMP imbalance in specific brain structures, which is tightly associated with a local inflammatory process as shown by the presence of immune infiltrating cells, differentially impairs CNS integrity and may contribute to the multiplicity of late neurological disorders observed in this viral mouse model.

scholarly journals A genetic mouse model of adult-onset, pervasive central nervous system demyelination with robust remyelination

Brain ◽  
2010 ◽  
Vol 133 (10) ◽  
pp. 3017-3029 ◽  
Author(s):  
Maria Traka ◽  
Kavin Arasi ◽  
Robin L. Avila ◽  
Joseph R. Podojil ◽  
Athena Christakos ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Adult Onset ◽  
Genetic Mouse Model ◽  
Central Nervous System Demyelination
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