L-Citrulline Level and Transporter Activity Are Altered in Experimental Models of Amyotrophic Lateral Sclerosis

Author(s):  
Asmita Gyawali ◽  
Shashi Gautam ◽  
Seung Jae Hyeon ◽  
Hoon Ryu ◽  
Young-Sook Kang
2020 ◽  
Vol 13 ◽  
Author(s):  
Mamtaj Alam ◽  
Rajeshwar Kumar Yadav ◽  
Elizabeth Minj ◽  
Aarti Tiwari ◽  
Sidharth Mehan

: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease (MND) characterised by the death of upper and lower motor neurons (corticospinal tract) in the motor cortex, basal ganglia, brain stem, and spinal cord. The patient experiences the sign and symptoms between 55 to 75 years of age included impaired motor movement, difficulty in speaking and swallowing, grip loss, muscle atrophy, spasticity and sometimes associated with memory and cognitive impairments. Median survival is 3 to 5 years after diagnosis and 5 to 10% beyond 10 years of age. The limited intervention of pharmacologically active compounds that are used clinically is majorly associated with the narrow therapeutic index. Pre-clinically established experimental models where neurotoxin methyl mercury mimics the ALS like behavioural and neurochemical alterations in rodents associated with neuronal mitochondrial dysfunctions and downregulation of adenyl cyclase mediated cAMP/CREB is the main pathological hallmark for the progression of ALS in central as well in the peripheral nervous system. Despite the considerable investigation into neuroprotection, it still constrains treatment choices to strong care and organization of ALS complications. Therefore, current review specially targeted in the investigation of clinical and pre-clinical features available for ALS to understand the pathogenic mechanisms and to explore the pharmacological interventions associated with up-regulation of intracellular adenyl cyclase/cAMP/CREB and mitochondrial-ETC coenzyme-Q10 activation as a future drug target in the amelioration of ALS mediated motor neuronal dysfunctions.


2016 ◽  
Vol 3 (2) ◽  
pp. e00023
Author(s):  
J. M. Gregory ◽  
F. M. Waldron ◽  
T. Soane ◽  
L. Fulton ◽  
D. Leighton ◽  
...  

2013 ◽  
Vol 21 (8) ◽  
pp. 1486-1496 ◽  
Author(s):  
Aikaterini Nanou ◽  
Adrian Higginbottom ◽  
Chiara F Valori ◽  
Matthew Wyles ◽  
Ke Ning ◽  
...  

Author(s):  
Alessia De Felice ◽  
Annamaria Confaloni ◽  
Alessio Crestini ◽  
Roberta De Simone ◽  
Fiorella Malchiodi-Albedi ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Agnese Gugliandolo ◽  
Placido Bramanti ◽  
Emanuela Mazzon

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons. Patients show both motor and extra-motor symptoms. A cure is not available at this time, and the disease leads to death within 3–5 years, mainly due to respiratory failure. Stem cell therapy is arising as a new promising approach for the treatment of neurodegenerative disorders. In particular, mesenchymal stem cells (MSCs) seem the most suitable type of stem cells, thanks to their demonstrated beneficial effects in different experimental models, to the easy availability, and to the lack of ethical problems. In this review, we focused on the studies involving ALS rodent models and clinical trials in order to understand the potential beneficial effects of MSC transplantation. In different ALS rodent models, the administration of MSCs induced a delay in disease progression and at least a partial recovery of the motor function. In addition, clinical trials evidenced the feasibility and safety of MSC transplantation in ALS patients, given that no major adverse events were recorded. However, only partial improvements were shown. For this reason, more studies and trials are needed to clarify the real effectiveness of MSC-based therapy in ALS.


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