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Profiles of Doctorate Dissertations
Research Relevance and Potential Impact
Neurodegeneration is a common feature of a large number of diseases that come under the
umbrella of “neurodegenerative diseases”; and involve loss of nerve structure and function.
The prevalence of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s
disease is increasing, but exact mechanisms and effective treatments are lacking. The burden
of these neurodegenerative diseases is growing, as the population ages, with huge economic
and human costs. Multiple components are linked to the pathogenesis of neurodegenerative
diseases including protein aggregation, mitochondrial dysfunction and oxidative stress, diet
components and neurotoxins, vascular disorders, excitotoxicity and neuroinflammation.
Neuroinflammation was considered as a passive response to neuronal damage. However,
several studies proved that inflammation may be a basic mechanism driving the progressive
nature of multiple neurodegenerative diseases. TNF-α, as a proinflammatory cytokine, exerts
both homeostatic and pathophysiological roles in the CNS. The present study was conducted
to elucidate the neuroprotective role of TNF-α in hippocampal neurodegeneration and to find
out the possible mechanisms for its effects. The results of this study added to the growing
knowledge about the multiple factors involved in the neurodegenerative process, specifically
excitotoxicity, neuroinflammation and oxidative stress. They also supported the growing
evidence showing that TNF-α confers protection for the neurons, specifically for hippocampal
neurons which are the focus of the study. Highlighting the neuroprotective side of TNF-α provides
an important factor to be considered for future studies on therapeutic approaches involving
complete neutralization of TNF-α for treatment of various disorders. We recommend that these
treatments should be examined on different areas of the brain to avoid the occurrence of side
effects that would arise from complete deactivation of the TNF signal-transduction cascade.
Relevant Publications
• Zhang, X. M., Zheng, X. Y., Sharkawi, S. S., Ruan, Y., Amir, N., Azimullah, S., Hasan, M.
Y., Zhu, J., Adem, A. (2013). Possible protecting role of TNF-alpha in kainic acid-induced
neurotoxicity via down-regulation of NFkappaB signaling pathway. Curr Alzheimer Res, 10(6),
660-669.
• Sharkawi, S. S. and Adem, A. (2016). Tumor necrosis factor alpha in kainic acid induced
neurodegeneration. International Conference in Educational Neuroscience (ICEN), Abu Dhabi,
UAE; February, 2016. (Poster Presentation).
• Sharkawi, S. S. and Adem, A. (2016). Effects of Tumor Necrosis Factor Alpha on Cytokines,