scholarly journals MRI CNS Atrophy Pattern and the Etiologies of Progressive Ataxias

2021 ◽  
Author(s):  
Mario Mascalchi
Keyword(s):  
Cerebellar Atrophy ◽  
Olivopontocerebellar Atrophy ◽  
Volume Loss ◽  
Cellular Targets ◽  
Inherited Ataxias ◽  
Genetic Assessment ◽  
Cortical Cerebellar Atrophy

MRI shows in-vivo the three archetypal patterns of CNS volume loss underlying progressive ataxias, namely spinal atrophy (SA), cortical cerebellar atrophy (CCA) and olivopontocerebellar atrophy (OPCA). The MRI-based CNS atrophy pattern was reviewed in 128 progressive ataxias. A CNS atrophy pattern was identified in 91 conditions: SA in Freidreich’s ataxia, CCA in 5 acquired and 72 (24 dominant, 47 recessive,1 X-linked) inherited ataxias, OPCA in Multi-System Atrophy and 12 (9 dominant, 2 recessive,1 X-linked) inherited ataxias. The MRI-based CNS atrophy pattern may be useful for genetic assessment, identification of shared cellular targets, and repurposing therapies or enlargement of drugs indications in progressive ataxias.

Reduced brain electric activities of frontal lobe in cortical cerebellar atrophy

2003 ◽  
Vol 114 (4) ◽  
pp. 740-747 ◽  
Author(s):  
Mio Arai ◽  
Hideaki Tanaka ◽  
Roberto D Pascual-Marqui ◽  
Koichi Hirata
Keyword(s):  
Frontal Lobe ◽  
Cerebellar Atrophy ◽  
Cortical Cerebellar Atrophy

The neural crest population responding to endothelin-3 in vitro includes multipotent cells

1997 ◽  
Vol 110 (14) ◽  
pp. 1673-1682 ◽  
Author(s):  
J.G. Stone ◽  
L.I. Spirling ◽  
M.K. Richardson
Keyword(s):  
Neural Crest ◽  
Schwann Cells ◽  
Cell Types ◽  
Developmental Potential ◽  
Colony Assay ◽  
Cellular Targets ◽  
Multipotent Cells ◽  
Endothelin 3

The peptide endothelin 3 (EDN3) is essential for normal neural crest development in vivo, and is a potent mitogen for quail truncal crest cells in vitro. It is not known which subpopulations of crest cells are targets for this response, although it has been suggested that EDN3 is selective for melanoblasts. In the absence of cell markers for different precursor types in the quail crest, we have characterised EDN3-responsive cell types using in vitro colony assay and clonal analysis. Colonies were analysed for the presence of Schwann cells, melanocytes, adrenergic cells or sensory-like cells. We provide for the first time a description of the temporal pattern of lineage segregation in neural crest cultures. In the absence of exogenous EDN3, crest cells proliferate and then differentiate. Colony assay indicates that in these differentiated cultures few undifferentiated precursors remain and there is a low replating efficiency. By contrast, in the presence of 100 ng/ml EDN3 differentiation is inhibited and most of the cells maintain the ability to give rise to mixed colonies and clones containing neural crest derivatives. A high replating efficiency is maintained. In secondary culture there was a progressive decline in the number of cell types per colony in control medium. This loss of developmental potential was not seen when exogenous EDN3 was present. Cell type analysis suggests two novel cellular targets for EDN3 under these conditions. Contrary to expectations, one is a multipotent precursor whose descendants include melanocytes, adrenergic cells and sensory-like cells; the other can give rise to melanocytes and Schwann cells. Our data do not support previous claims that the action of EDN3 in neural crest culture is selective for cells in the melanocyte lineage.

In vivo proof-of-concept for two experimental antiviral drugs, both directed to cellular targets, using a murine cytomegalovirus model

2019 ◽  
Vol 161 ◽  
pp. 63-69 ◽  
Author(s):  
Eric Sonntag ◽  
Friedrich Hahn ◽  
Luca D. Bertzbach ◽  
Lisa Seyler ◽  
Christina Wangen ◽  
...  
Keyword(s):  
Antiviral Drugs ◽  
Murine Cytomegalovirus ◽  
Proof Of Concept ◽  
Cellular Targets

scholarly journals Dynamic Cerebrospinal Fluid Flow on MRI in Cortical Cerebellar Atrophy and Multiple System Atrophy-cerebellar Type

2015 ◽  
Vol 54 (14) ◽  
pp. 1717-1723 ◽  
Author(s):  
Yusuke Fukui ◽  
Nozomi Hishikawa ◽  
Kota Sato ◽  
Syoichiro Kono ◽  
Kosuke Matsuzono ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Multiple System Atrophy ◽  
Cerebellar Atrophy ◽  
Cerebrospinal Fluid Flow ◽  
Cerebellar Type ◽  
Cortical Cerebellar Atrophy

scholarly journals Outcomes of Progranulin Gene Therapy in the Retina are Dependent on Time of Delivery

2021 ◽  
Author(s):  
Emilia A. Zin ◽  
Daisy Han ◽  
Jennifer Tran ◽  
Nikolas Morisson-Welch ◽  
Meike Visel ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Quantitative Methods ◽  
Vision Loss ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Cerebellar Atrophy ◽  
Gene Replacement ◽  
Therapeutic Benefit ◽  
Lysosomal Function ◽  
Knockout Mouse Model

AbstractNeuronal ceroid lipofuscinosis (NCL) is a family of neurodegenerative diseases caused by mutations to genes related to lysosomal function. One variant, CNL11, is caused by mutations to the gene encoding the protein progranulin. Primarily secreted by microglia, progranulin regulates neuronal lysosomal function once endocytosed. Absence of progranulin causes cerebellar atrophy, seizures, ataxia, dementia and vision loss. As progranulin gene therapies targeting the brain are developed, it is also advantageous to focus on the retina, as its characteristics are beneficial for gene therapy development: the retina is easily visible through direct imaging, can be assessed through quantitative methods in vivo, requires smaller amounts of AAV and AAV can be administered via a less invasive surgery. In this study we characterize the retinal degeneration in a progranulin knockout mouse model of CLN11 and study the effects of gene replacement at different time points. All mice heterologously expressing progranulin showed reduction in lipofuscin deposits and microglia infiltration. While mice that receive systemic AAV9.2YF-scCAG-PGRN at post-natal day 3 or 4 show a reduction in retina thinning, mice injected intravitreally at months 1 and 6 with 7m8-scCAG-PGRN show no improvement, and mice injected at 12 months of age show increased retinal thinning in comparison to their controls. Thus, delivery of progranulin proves to be time-sensitive, requiring early administration for optimal therapeutic benefit.

scholarly journals Interfacial Peptides as Affinity Modulating Agents of Protein-Protein Interactions

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 106
Author(s):  
Pavel V. Ershov ◽  
Yuri V. Mezentsev ◽  
Alexis S. Ivanov
Keyword(s):  
Protein Interactions ◽  
Targeted Delivery ◽  
Protein Complexes ◽  
Protein Protein Interactions ◽  
Good Efficiency ◽  
Cellular Targets ◽  
Proteolytic Stability ◽  
Clinically Significant

The identification of disease-related protein-protein interactions (PPIs) creates objective conditions for their pharmacological modulation. The contact area (interfaces) of the vast majority of PPIs has some features, such as geometrical and biochemical complementarities, “hot spots”, as well as an extremely low mutation rate that give us key knowledge to influence these PPIs. Exogenous regulation of PPIs is aimed at both inhibiting the assembly and/or destabilization of protein complexes. Often, the design of such modulators is associated with some specific problems in targeted delivery, cell penetration and proteolytic stability, as well as selective binding to cellular targets. Recent progress in interfacial peptide design has been achieved in solving all these difficulties and has provided a good efficiency in preclinical models (in vitro and in vivo). The most promising peptide-containing therapeutic formulations are under investigation in clinical trials. In this review, we update the current state-of-the-art in the field of interfacial peptides as potent modulators of a number of disease-related PPIs. Over the past years, the scientific interest has been focused on following clinically significant heterodimeric PPIs MDM2/p53, PD-1/PD-L1, HIF/HIF, NRF2/KEAP1, RbAp48/MTA1, HSP90/CDC37, BIRC5/CRM1, BIRC5/XIAP, YAP/TAZ–TEAD, TWEAK/FN14, Bcl-2/Bax, YY1/AKT, CD40/CD40L and MINT2/APP.

Cortical Cerebellar Atrophy without Ataxia

1946 ◽  
Vol 5 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Ben W. Lichtenstein ◽  
Samuel A. Levinson
Keyword(s):  
Cerebellar Atrophy ◽  
Cortical Cerebellar Atrophy

scholarly journals In Vivo Disintegration of Four Different Luting Agents

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Deniz Gemalmaz ◽  
Cornelis H. Pameijer ◽  
Mark Latta ◽  
Ferah Kuybulu ◽  
Toros Alcan
Keyword(s):  
Zinc Phosphate ◽  
Rank Order ◽  
Glass Ionomer Cement ◽  
Resin Cement ◽  
Volume Loss ◽  
Glass Ionomer ◽  
Optical Scanner ◽  
Luting Agents ◽  
Significant Difference

The purpose of this study was to evaluate the disintegration of luting agents. An intraoral sample holder was made having four holes of 1.4 mm diameter and 2 mm depth. The holder was soldered onto the buccal surface of an orthodontic band, which was cemented to the first upper molar in 12 patients, average age 26 years. The holes were filled with a zinc phosphate (Phosphate Kulzer), a glass ionomer (Ketac Cem), a resin-modified-glass ionomer (Fuji Plus), and a resin cement (Calibra). Impressions were made at baseline, and 6, 12, and 18 months from which epoxy replicas were made, which were scanned with an optical scanner. Total volume loss was calculated. The rank order of mean volume loss was as follows: Phosphate cement > Ketac Cem = Fuji Plus = Calibra. Cement type and time had statistically significant effects on volume loss of cements (P<0.001). Under in vivo conditions, zinc phosphate cement disintegrated the most, whereas no significant difference was observed for glass ionomer and resin-based cements. As intraoral conditions are considerably less aggressive than experimental laboratory conditions, the erosion behavior of glass ionomer cement was found to be similar to the resin-based cements in contradiction to previous laboratory results.

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