Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytidine-5-diphosphocholine (CDP-choline, citicoline) is an endogenous nucleoside involved in generation of phospholipids, membrane formation and its repair. It demonstrates beneficial effects in certain central nervous system injury models, including cerebral ischaemia, neurodegenerative disorders and spinal cord injury. Defective neuronal and/or glial glutamate transport is claimed to contribute to progressive loss of motor neurons (MNs) in amyotrophic lateral sclerosis (ALS). Our previous ultrastructural studies, performed on an organotypic tissue culture model of chronic glutamate excitotoxicity, documented a subset of various modes of MN death including necrotic, apoptotic and autophagocytic cell injury. The aim of this ultrastructural study was to determine the potential neuroprotective effect of CDP-choline on neuronal changes in a glutamate excitotoxic ALS model in vitro. Organotypic cultures of the rat lumbar spinal cord subjected to 100 microM DL-threo-beta-hydroxyaspartate (THA) were pretreated with 100 microM of CDP-choline. The exposure of spinal cord cultures to CDP-choline and THA distinctly reduced the development of typical apoptotic changes, whereas both necrotic and autophagocytic THA-induced MN injury occurred. These results indicate that CDP-choline treatment might exert a neuroprotective effect against neuronal apoptotic changes in a model of chronic excitotoxicity in vitro.
 ...
PMID:CDP-choline protects motor neurons against apoptotic changes in a model of chronic glutamate excitotoxicity in vitro. 1858 8

Important pathogenic factors in ALS include excitotoxicity and oxidative stress. Cytidine 5-diphosphocholine (CDP-choline) has recently been reported to have neuroprotective effects in animal models for neurodegenerative diseases, attributable to its anti-glutamatergic, anti-excitotoxic, anti-apoptotic and membrane-preserving properties. In this study we administered either CDP-choline or vehicle to transgenic SOD1-G93A mice daily via intraperitoneal (i.p.) injection starting before disease onset (day 30). By monitoring of survival, motor function, weight and general condition we examined possible therapeutic effects. Additional animals were used for histological studies to determine the effect of CDP-choline on motor neuron survival, astrocytosis and myelination in the spinal cord. Results showed that CDP-choline treatment modified neither the deterioration of general condition nor the loss of body weight. Survival of CDP-choline treated animals was not prolonged compared to vehicle treated controls. None of the behavioural motor function tests revealed differences between groups and no differences in motor neuron survival, astrocytosis or myelination were detected by histological analyses. In conclusion, our data from the transgenic mouse model do not strongly support further clinical validation of CDP-choline for the treatment of ALS.
 ...
PMID:CDP-choline is not protective in the SOD1-G93A mouse model of ALS. 2328 44

Genome editing tools have rapidly been adopted by plant scientists for gene function discovery and crop improvement. The current technical challenge is to efficiently induce precise and predictable targeted point mutations valuable for crop breeding purposes. Cytidine base editors (CBEs) are CRISPR/Cas9 derived tools recently developed to direct a C-to-T base conversion. Stable genomic integration of CRISPR/Cas9 components through Agrobacterium-mediated transformation is the most widely used approach in dicotyledonous plants. However, elimination of foreign DNA may be difficult to achieve, especially in vegetatively propagated plants. In this study, we targeted the acetolactate synthase (ALS) gene in tomato and potato by a CBE using Agrobacterium-mediated transformation. We successfully and efficiently edited the targeted cytidine bases, leading to chlorsulfuron-resistant plants with precise base edition efficiency up to 71% in tomato. More importantly, we produced 12.9% and 10% edited but transgene-free plants in the first generation in tomato and potato, respectively. Such an approach is expected to decrease deleterious effects due to the random integration of transgene(s) into the host genome. Our successful approach opens up new perspectives for genome engineering by the co-edition of the ALS with other gene(s), leading to transgene-free plants harboring new traits of interest.
 ...
PMID:Transgene-Free Genome Editing in Tomato and Potato Plants Using Agrobacterium-Mediated Delivery of a CRISPR/Cas9 Cytidine Base Editor. 3066 98