Omar Hamza

Introduction. Alzheimer’s disease (AD) is one of the most common neurocognitively degenerating diseases, affecting about 40% of anyone past the age of 80¹. Patients affected by AD demonstrate weaker synapse strength, significant neuronal cell loss, memory deficits, and overall cognitive dysfunction. Many of these negative effects are mediated by amyloid beta plaque buildup that leads to a modulation in a variety of cytokines, such as an increase in apoptosis and inflammation^2,3. Fibronectin Type III Domain Containing 5 (FNDC5, the precursor to the irisin protein) has been demonstrated to reverse the effects of the amyloid beta plaques as well as improve overall cognition⁴. However, in patients with AD, levels of FNDC5/irisin are much lower⁴. Methods. To assess the mechanism of FNDC5/irisin, mice were subjected to middle cerebral artery occlusion and then injected with irisin⁵. Mice were subjected to various tests like novel object recognition and other memory tests⁵. Other methods included various exercise types to assess how exercise reverses neurocognitive decline. Levels of FNDC5/irisin and most factors were assessed using PCR. Results. After injection with irisin, brain infarct volumes were decreased as well as a downregulation of Bax and caspase-3, upregulation of BCL-2, decreased TNF-alpha and IL-6, and increased phosphorylation of ERK 1/2 and Akt were all demonstrated⁵. This indicates a decrease in apoptosis and inflammation directly resulting from the injection of irisin. Novel object recognition was assessed and mice with AD performed poorly compared to mice injected with irisin⁴. An optimal injection of 7.5 micrograms of irisin per kilogram of body weight was determined⁷. Exercise also demonstrated neurocognitive benefits that reversed amyloid beta effects, very similar to the effects of irisin injection⁴. Mice were subjected to continuous and interval exercise regimens. Short hairpin knockout of FNDC5 was conducted on these mice. All the neurological recovery demonstrated after exercise was reversed, proving that FNDC5/irisin is directly responsible for the neurological recovery in mice undergoing exercise⁴. This demonstrated how exercise increases FNDC5/irisin. Interval training proved to be the most effective form of exercise and increased levels of FNDC5/irisin the most⁶.  Conclusion. Injection with irisin and interval training proved to reverse the apoptotic factors that AD causes. Exercise increases levels of FNDC5/irisin which effectively decrease apoptotic factors and inflammation.

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