Abstract
Amyotrophic lateral sclerosis (ALS) is a common degenerative disease of the central nervous system concerning a progressive loss of upper and lower motor neurons. While 5%–10% of patients are diagnosed with the inherited form of the disease, the vast majority of patients suffer from the less characterized sporadic form of ALS (sALS). As the wobbler mouse and the ALS show striking similarities in view of phenotypical attributes, the mouse is rated as an animal model for the disease. Recent investigations show the importance of nicotinamide adenine dinucleotide (NAD+) and its producing enzyme nicotinic acid mononucleotide transferase 2 (Nmnat2) for neurodegeneration as well as for the preservation of health of the neuronal cells. Furthermore, it is newly determined that these molecules show significant downregulations in the spinal cord of wobbler mice in the stable phase of disease development. Here, we were able to prove a positive benefit on affected motor neurons from an additional NAD+ supply as well as an increase in the Nmnat2 level through caffeine treatment in cells in vitro. In addition, first assumptions about the importance of endogenous and exogenous factors that have an influence on the wellbeing of motor nerve cells in the model of ALS can be considered.
Highlights
Amyotrophic lateral sclerosis (ALS) is the most common adult onset motor neuron disease
Since the NAD+ level was proved to be reduced in the cervical spinal cord of wobbler mice at p40 due to a significant downregulation of Nmnat2 [18], we aimed to investigate the impact of a NAD+
Due to the isolation of the spinal cord and the isolated cultivation of the cells in vitro, motor neurons do not experience any influences from attached cells, so that predominantly endogenous factors determine the development of the like
Summary
Amyotrophic lateral sclerosis (ALS) is the most common adult onset motor neuron disease. It is characterized by a degeneration of motor neurons in the brain and in the spinal cord [1]. The clinical phenotype involves weakness and atrophy as well as hyperreflexia and increased muscle tone [2]. While about 10% of the ALS cases represent the familial form, the disease occurs primarily sporadic [3]. A primarily, not exclusively, anti-excitotoxic drug, and edaravone, an antioxidant, have only a minor beneficial impact on the course of the disease in a limited population of patients. The results on ropinirole, a dopamine receptor agonist, on ALS-derived iPSCs as a novel drug are not yet complete but auspicious [5]
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