scholarly journals Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease

10.1038/78682 ◽  
2000 ◽  
Vol 6 (8) ◽  
pp. 916-919 ◽  
Author(s):  
Frédérique Bard ◽  
Catherine Cannon ◽  
Robin Barbour ◽  
Rae-Lyn Burke ◽  
Dora Games ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Alzheimer Disease ◽  
Mouse Model ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
The Central Nervous System

scholarly journals Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease

2015 ◽  
Vol 291 (4) ◽  
pp. 1905-1920 ◽  
Author(s):  
Brian Spencer ◽  
Rewati Potkar ◽  
Jeff Metcalf ◽  
Ivy Thrin ◽  
Anthony Adame ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Alzheimer Disease ◽  
Mouse Model ◽  
Neuropeptide Y ◽  
Targeted Delivery ◽  
Lentiviral Vector ◽  
Receptor Expression ◽  
Neural Precursor ◽  
The Central Nervous System

Neuropeptide Y (NPY) is one of the most abundant protein transmitters in the central nervous system with roles in a variety of biological functions including: food intake, cardiovascular regulation, cognition, seizure activity, circadian rhythms, and neurogenesis. Reduced NPY and NPY receptor expression is associated with numerous neurodegenerative disorders including Alzheimer disease (AD). To determine whether replacement of NPY could ameliorate some of the neurodegenerative and behavioral pathology associated with AD, we generated a lentiviral vector expressing NPY fused to a brain transport peptide (apoB) for widespread CNS delivery in an APP-transgenic (tg) mouse model of AD. The recombinant NPY-apoB effectively reversed neurodegenerative pathology and behavioral deficits although it had no effect on accumulation of Aβ. The subgranular zone of the hippocampus showed a significant increase in proliferation of neural precursor cells without further differentiation into neurons. The neuroprotective and neurogenic effects of NPY-apoB appeared to involve signaling via ERK and Akt through the NPY R1 and NPY R2 receptors. Thus, widespread CNS-targeted delivery of NPY appears to be effective at reversing the neuronal and glial pathology associated with Aβ accumulation while also increasing NPC proliferation. Overall, increased delivery of NPY to the CNS for AD might be an effective therapy especially if combined with an anti-Aβ therapeutic.

scholarly journals Serotonin Promotes Serum Albumin Interaction with the Monomeric Amyloid β Peptide

2021 ◽  
Vol 22 (11) ◽  
pp. 5896
Author(s):  
Ekaterina A. Litus ◽  
Alexey S. Kazakov ◽  
Evgenia I. Deryusheva ◽  
Ekaterina L. Nemashkalova ◽  
Marina P. Shevelyova ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Central Nervous System ◽  
Nervous System ◽  
Serum Albumin ◽  
Quaternary Structure ◽  
Amyloid Β ◽  
Resonance Spectroscopy ◽  
Amyloid Β Peptide ◽  
Structural Differences ◽  
The Central Nervous System

Prevention of amyloid β peptide (Aβ) deposition via facilitation of Aβ binding to its natural depot, human serum albumin (HSA), is a promising approach to preclude Alzheimer’s disease (AD) onset and progression. Previously, we demonstrated the ability of natural HSA ligands, fatty acids, to improve the affinity of this protein to monomeric Aβ by a factor of 3 (BBRC, 510(2), 248–253). Using plasmon resonance spectroscopy, we show here that another HSA ligand related to AD pathogenesis, serotonin (SRO), increases the affinity of the Aβ monomer to HSA by a factor of 7/17 for Aβ40/Aβ42, respectively. Meanwhile, the structurally homologous SRO precursor, tryptophan (TRP), does not affect HSA’s affinity to monomeric Aβ, despite slowdown of the association and dissociation processes. Crosslinking with glutaraldehyde and dynamic light scattering experiments reveal that, compared with the TRP-induced effects, SRO binding causes more marked changes in the quaternary structure of HSA. Furthermore, molecular docking reveals distinct structural differences between SRO/TRP complexes with HSA. The disintegration of the serotonergic system during AD pathogenesis may contribute to Aβ release from HSA in the central nervous system due to impairment of the SRO-mediated Aβ trapping by HSA.

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 Endogenous Cu in the central nervous system fails to satiate the elevated requirement for Cu in a mutant SOD1 mouse model of ALS

Metallomics ◽  
2016 ◽  
Vol 8 (9) ◽  
pp. 1002-1011 ◽  
Author(s):  
J. B. Hilton ◽  
A. R. White ◽  
P. J. Crouch
Keyword(s):  
Central Nervous System ◽  
Amyotrophic Lateral Sclerosis ◽  
Nervous System ◽  
Mouse Model ◽  
Limited Capacity ◽  
Mutant Sod1 ◽  
The Central Nervous System ◽  
Sod1 Mouse ◽  
Lateral Sclerosis

It is unclear why ubiquitous expression of mutant SOD1 selectively affects the central nervous system in amyotrophic lateral sclerosis. Here we hypothesise that the central nervous system is primarily affected because, unlike other tissues, it has relatively limited capacity to satiate an increased requirement for Cu.

scholarly journals A Japanese Encephalitis Virus Genotype 5 Molecular Clone Is Highly Neuropathogenic in a Mouse Model: Impact of the Structural Protein Region on Virulence

2015 ◽  
Vol 89 (11) ◽  
pp. 5862-5875 ◽  
Author(s):  
Mélissanne de Wispelaere ◽  
Marie-Pascale Frenkiel ◽  
Philippe Desprès
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Viral Clearance ◽  
The Central Nervous System ◽  
Genotype 5

ABSTRACTJapanese encephalitis virus (JEV) strains can be separated into 5 genotypes (g1 to g5) based on sequence similarity. JEV g5 strains have been rarely isolated and are poorly characterized. We report here the full characterization of a g5 virus generated using a cDNA-based technology and its comparison with a widely studied g3 strain. We did not observe any major differences between those viruses when their infectious cycles were studied in various cell linesin vitro. Interestingly, the JEV g5 strain was highly pathogenic when inoculated to BALB/c mice, which are known to be largely resistant to JEV g3 infection. The study of chimeric viruses between JEV g3 and g5 showed that there was a poor viral clearance of viruses that express JEV g5 structural proteins in BALB/c mice blood, which correlated with viral invasion of the central nervous system and encephalitis. In addition, using anin vitromodel of the blood-brain barrier, we were able to show that JEV g5 does not have an enhanced capacity for entering the central nervous system, compared to JEV g3. Overall, in addition to providing a first characterization of the understudied JEV g5, our work highlights the importance of sustaining an early viremia in the development of JEV encephalitis.IMPORTANCEGenotype 5 viruses are genetically and serologically distinct from other JEV genotypes and can been associated with human encephalitis, which warrants the need for their characterization. In this study, we characterized thein vitroandin vivoproperties of a JEV g5 strain and showed that it was more neuropathogenic in a mouse model than a well-characterized JEV g3 strain. The enhanced virulence of JEV g5 was associated with poor viral clearance but not with enhanced crossing of the blood-brain barrier, thus providing new insights into JEV pathogenesis.

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