Neuronal Protection: Insights from Nerve Growth Factor NGF Gene Expression Analysis in Alzheimer's Disease Management
DOI:
https://doi.org/10.61919/jhrr.v4i1.720Keywords:
Cognitive Impairment, Dementia, Expression Analysis, Neurobiology, Neuroprotection, NGFAbstract
Background: Dementia encompasses a spectrum of neurological disorders, prominently featuring Alzheimer's disease (AD), which constitutes approximately 70% of all dementia cases. Risk factors include genetic predispositions, such as the ApoE ε4 allele, APP, PSEN1/PSEN2, and lifestyle or health-related factors like depression, smoking, hypertension, and Type II diabetes. The latter is notably associated with conditions like hyperglycemia or insulin resistance, which potentially disrupt cerebral function and precipitate cognitive decline.
Objective: This study focuses on the Nerve Growth Factor (NGF) genes, exploring their role in neuroprotection. Specifically, it examines the expression levels of the NGF gene in diabetic patients with dementia and correlates these findings with neural disturbances as gauged by Mini Mental State Examination (MMSE) scores.
Methods: Blood samples (5 ml each) were collected from 100 participants, comprising 68 cases of diabetic dementia and 32 healthy controls, from Jinnah Hospital Lahore and Shaikh Zayed Hospital Lahore. The study involved nucleic acid extraction, primer design and optimization, and targeted RT-qPCR for NGF expression analysis. ELISA and MMSE scoring were also employed to assess cognitive impairment.
Results: Analysis revealed significantly lower NGF expression in the diabetic dementia group compared to controls. Specifically, an NGF gene expression decrease correlated with cognitive impairment severity; 80% of participants scored below 9 on the MMSE, indicative of severe dementia. A Pearson’s correlation coefficient of 0.494 underscored the relationship between NGF expression and cognitive impairment.
Conclusion: The findings highlight the potential role of NGF genes in the pathogenesis of dementia among individuals with diabetes. Changes in NGF expression may be pivotal in dementia development, suggesting that NGF could serve as a biomarker for the diagnosis and potentially guide therapeutic strategies.
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References
Saedi, E., Gheini, M. R., Faiz, F., & Arami, M. A. (2016). Diabetes mellitus and cognitive impairments. World journal of diabetes, 7(17), 412–422.
Quan, M., Cao, S., Wang, Q., Wang, S., & Jia, J. (2023). Genetic Phenotypes of Alzheimer's Disease: Mechanisms and Potential Therapy. Phenomics (Cham, Switzerland), 3(4), 333–349
Islam, S., Sun, Y., Gao, Y., Nakamura, T., Noorani, A. A., Li, T., Wong, P. C., Kimura, N., Matsubara, E., Kasuga, K., Ikeuchi, T., Tomita, T., Zou, K., & Michikawa, M. (2022). Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience, 42(8), 1574–1586.
Ochalek, A., Mihalik, B., Avci, H. X., Chandrasekaran, A., Téglási, A., Bock, I., Giudice, M. L., Táncos, Z., Molnár, K., László, L., Nielsen, J. E., Holst, B., Freude, K., Hyttel, P., Kobolák, J., & Dinnyés, A. (2017). Neurons derived from sporadic Alzheimer's disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation. Alzheimer's research & therapy, 9(1), 90.
Quan, M., Cao, S., Wang, Q., Wang, S., & Jia, J. (2023). Genetic Phenotypes of Alzheimer's Disease: Mechanisms and Potential Therapy. Phenomics (Cham, Switzerland), 3(4), 333–349.
Samario-Román, J., Larqué, C., Pánico, P., Ortiz-Huidobro, R. I., Velasco, M., Escalona, R., & Hiriart, M. (2023). NGF and Its Role in Immunoendocrine Communication during Metabolic Syndrome. International journal of molecular sciences, 24(3), 1957.
Hölscher C. (2019). Insulin Signaling Impairment in the Brain as a Risk Factor in Alzheimer's Disease. Frontiers in aging neuroscience, 11, 88.
Abubakar, M. B., Sanusi, K. O., Ugusman, A., Mohamed, W., Kamal, H., Ibrahim, N. H., Khoo, C. S., & Kumar, J. (2022). Alzheimer's Disease: An Update and Insights Into Pathophysiology. Frontiers in aging neuroscience, 14, 742408.
Do Carmo, S., Kannel, B., & Cuello, A. C. (2021). The Nerve Growth Factor Metabolic Pathway Dysregulation as Cause of Alzheimer's Cholinergic Atrophy. Cells, 11(1), 16.
Pentz, R., Iulita, M. F., Ducatenzeiler, A., Bennett, D. A., & Cuello, A. C. (2021). The human brain NGF metabolic pathway is impaired in the pre-clinical and clinical continuum of Alzheimers disease. Molecular psychiatry, 26(10), 6023–6037.
Abubakar, M. B., Sanusi, K. O., Ugusman, A., Mohamed, W., Kamal, H., Ibrahim, N. H., Khoo, C. S., & Kumar, J. (2022). Alzheimer's Disease: An Update and Insights Into Pathophysiology. Frontiers in aging neuroscience, 14, 742408.
Barloese, M. C. J., Bauer, C., Petersen, E. T., Hansen, C. S., Madsbad, S., & Siebner, H. R. (2022). Neurovascular Coupling in Type 2 Diabetes With Cognitive Decline. A Narrative Review of Neuroimaging Findings and Their Pathophysiological Implications. Frontiers in endocrinology, 13, 874007.
Spinelli, M., Fusco, S., & Grassi, C. (2019). Brain Insulin Resistance and Hippocampal Plasticity: Mechanisms and Biomarkers of Cognitive Decline. Frontiers in neuroscience, 13, 788.
Sherwani, S. I., Khan, H. A., Ekhzaimy, A., Masood, A., & Sakharkar, M. K. (2016). Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomarker insights, 11, 95–104.
Rajmohan, R., & Reddy, P. H. (2017). Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer's disease Neurons. Journal of Alzheimer's disease : JAD, 57(4), 975–999.
Rajmohan, R., & Reddy, P. H. (2017). Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer's disease Neurons. Journal of Alzheimer's disease : JAD, 57(4), 975–999.
Bruno, F., Abondio, P., Montesanto, A., Luiselli, D., Bruni, A. C., & Maletta, R. (2023). The Nerve Growth Factor Receptor (NGFR/p75NTR): A Major Player in Alzheimer's Disease. International journal of molecular sciences, 24(4), 3200.
Shen, L. L., Li, W. W., Xu, Y. L., Gao, S. H., Xu, M. Y., Bu, X. L., Liu, Y. H., Wang, J., Zhu, J., Zeng, F., Yao, X. Q., Gao, C. Y., Xu, Z. Q., Zhou, X. F., & Wang, Y. J. (2019). Neurotrophin receptor p75 mediates amyloid β-induced tau pathology. Neurobiology of disease, 132, 104567.
Bradshaw, R. A., Pundavela, J., Biarc, J., Chalkley, R. J., Burlingame, A. L., & Hondermarck, H. (2015). NGF and ProNGF: Regulation of neuronal and neoplastic responses through receptor signaling. Advances in biological regulation, 58, 16–27.
Dedoni, S., Olianas, M. C., Ingianni, A., & Onali, P. (2014). Type I interferons up-regulate the expression and signalling of p75 NTR/TrkA receptor complex in differentiated human SH-SY5Y neuroblastoma cells. Neuropharmacology, 79, 321–334.
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