RECREATIONIST

BEAUTIFUL….

On Cytokine Storms and Relative Treatment Options

As mentioned during last week’s discussion, a cytokine storm (hypercytokinemia) (CS) is a rogue immune reaction. Symptoms include fever, swelling and redness, fatigue and nausea, and sometimes result in fatality. When fighting pathogens, cytokines signal immune cells (T-cells, macrophages) to flood the site of infection, while stimulating further cytokine production through other cells. Normally the body regulates that feedback loop; however, if the reaction is out of control, too many immune cells flood a single place. The hyper-response may be attributed to a powerful, new pathogenic entity. The cytokine storm will continue to attack the pathogen without control, damaging tissue and or organs in the process.

Hypercytokinemia is characterized by the systematic disbandment of healthy immune cells (+/- 150 known inflammatory mediators). Both inflammatory and anti-inflammatory mediators, however, are elevated in the serum of patients experiencing a CS. Several diseases, such as graft versus host disease (GVHD), avian influenza and smallpox, trigger cytokine storms. Experimental drugs, such as trial drug TGN1412, also trigger CS alongside other serious symptoms.  Clinical trials evaluated corticosteroids and NSAIDs, commonly employed anti-CS treatments, and proved ineffective, but gemfibrozil, a pro-inflammatory cytokine inhibiting agent, proved clinically useful for decreasing lipids and increasing survival rates in influenza-infected mice. If its principle effects apply to humans, the drug may be quickly adapted as a treatment against influenza and derivatives of H5N1 strains.
 

Zahra Alamire  

On Anterograde and Retrograde Axonal Transport, Motor Neuron Diseases, and Stem Cells

            Axoplasmic Transport (axonal transport) is the cellular process responsible for the bidirectional movement of proteins, lipids, mitochondria, and other organelles between a neuron and cell body. This takes place through the cytoplasm of its axon (axoplasm).  Anterograde axonal transport is movement of molecules or organelles from the cell body to the synapse (space between the end of one neuron (terminal buttons) to the head of another (dendrites)). The movement of individual “cargoes” in Anterograde transport is mediated by kinesins, or a specific motor protein. Several kinesins lead to slower transport, although the mechanism or entity for the pauses in transit is unknown. There are two classes of slow anterograde transport: slow competent a (SCa), which carries microtubules and neurofilamnets (intermediate filaments found in neurons), and slow component b (SCb), which carries actin.

Neuron function and survival relies on the transport of material between extensive neuronal processes and the cell body. Deficits in axonal transport contribute to the pathogenesis (the production and development) of several neurodegenerative diseases, such as ALS, or amyotrophic lateral sclerosis. Recent studies reveal defects in dynein-mediated retrograde axonal transport are involved in ALS etiology, or ALS origination. Dynein is a motor protein (or motor molecule) in cells which convert chemical energy into the mechanical energy of movement. In a paper by L.J. Hayward, professor of the Department of Molecular and Cellular Biochemistry at the University of Kentucky, he discusses how mutant copper-zinc superoxide dismutase (SOD1) (an abundant enzyme in cells that safeguards cells from metabolic waste) and an irregular interaction between mutant SOD1 and dynein disturbs retrograde axonal transport of neurotrophic factors and mitochondria. Hayward also discussed a possible contribution of axonal transport to the aggregation and degradation process of mutant SOD1, and considered how the interference with axonal transport and protein turnover (protein accretion; balance between protein synthesis and protein degradation) by mutant SOD1 could influence the function of motor neurons in ALS.

The consequences of interrupted axoplasmic transport for vital proteins and material also leads to neurodegenerative diseases like Alzheimer’s, and indirectly affect individuals with cancer. Cancer drugs are notorious for altering microtubules, and therefore damaging never cells, because they are necessary for cell division. That leads back to stem cell therapy, the most promising solution to defects in axonal transport, and therefore any disease or cancer that destroys neurons.

Zahra Alamire

I have a City Headache, Scott Matthews.