In this two-part study, I investigated whether the cyclic-adenosine monophosphate response element-binding (CREB) protein has the potential to be clinically modulated as a therapeutic target for the treatment of neurodegenerative diseases. Part one consisted of a systematic review that was conducted on select articles gathered through a stepwise method to explore (1) the relationship between diseased, neurodegenerative brains and levels of active, phosphorylated CREB (pCREB), (2) increased activation of CREB as a treatment for neurodegenerative symptoms, and (3) a potential therapeutic drug for neurodegenerative diseases that can target CREB signaling. The results of the systematic review showed evidence that suggested excitotoxic concentrations of N-methyl-D-aspartate (NMDA) results in decreased pCREB levels, while decreased pCREB levels were associated with impaired cognition and behavior, increased cell death, as well as decreased CRE-gene transcription and long-term potentiation (LTP). Part two consisted of a systematic review and meta-analysis on clinical trials that used the phosphodiesterase type IV inhibitor, roflumilast, on healthy and schizophrenic patients. It was found that 100 µM roflumilast was able to improve verbal learning in healthy and schizophrenic subjects (ES = 64). Initial evidence indicates that future research on neurodegenerative diseases should further investigate CREB’s potential to be clinically modulated and research investigating PDE4 inhibitor drug therapy for the treatment of neurodegeneration should be expanded upon further in subsequent studies.
Bachelor of Science (B.S.)
College of Medicine
Burnett School of Biomedical Sciences
Sarmast, Mani, "A Systematic Review and Meta-Analysis of the Relationship Between the CREB Protein's Neuroplastic Functions and the Implications in Neurodegenerative Diseases: A Possible Link Between Synaptic Plasticity and Neurodegenerative Diseases" (2022). Honors Undergraduate Theses. 1203.