مقالات پذیرفته شده در هفتمین کنگره بین المللی زیست پزشکی
Assessment of the palmitic acid effect on neural cell lines in Alzheimer’s disease: with a comprehensive focus on signaling pathways
Assessment of the palmitic acid effect on neural cell lines in Alzheimer’s disease: with a comprehensive focus on signaling pathways
Sayed Mehrdad Azimi,1,*Hamid Bahramian,2Maedeh Moghadas,3
1. Department of Anatomical and Molecular Biology Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 2. Department of Anatomical and Molecular Biology Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 3. Department of Anatomical and Molecular Biology Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Introduction: Alzheimer's disease (AD) is characterized by progressive neurodegeneration and cognitive decline. While the exact causes remain unclear, there is increasing evidence that dietary and metabolic factors are implicated in AD pathogenesis. Saturated fatty acids such as palmitic acid (PA), the most common saturated fatty acid in the Western diet, have been shown to have noxious effects on neuronal health. PA can induce neurotoxicity by increasing oxidative stress, altering amyloid precursor protein processing, and promoting tau phosphorylation. In vitro studies with neuronal cell lines have demonstrated that consumption of PA can impair neuronal viability, plasticity, mitochondrial function, etc. through several potential mechanisms, including endoplasmic reticulum stress, autophagy dysregulation, and activation of inflammatory pathways. Comprehensive assessment across diverse neural cell models is necessary to elucidate the effects of PA on neurons and glial cells that underlie AD development. This review evaluates deleterious actions of PA in neural cells with a comprehensive concentration on signaling pathways which is crucial to elucidating diet-derived risk factors and guiding new preventative approaches for AD.
Methods: This review was conducted for articles published in ScienceDirect, Scopus, and PubMed from January 1, 2017, to December 31, 2022. The search strategy was performed using a combination of terms based on palmitic acid, neural cell lines, Alzheimer’s disease, and other related words for titles/abstracts. Two independent reviewers skimmed the titles and abstracts for eligibility criteria and relevant articles were included. Unrelated and non-English articles were excluded and a table was designated for excluded articles.
Results: PA has effects on neural cells and has been implicated in the pathogenesis of AD. It disrupts several signaling pathways involved in homeostasis, metabolism, plasticity, protein aggregation and phosphorylation, and neuronal survival, and can lead to AD neurodegeneration. These signaling pathways include the following: (1) the endoplasmic reticulum (ER) stress pathway disrupts ER calcium homeostasis and protein folding, leading to activation of the unfolded protein response. (2) Inflammatory pathways involving NF-κB and MAPK signaling in astrocytes and microglia. These cells release cytokines, which cause neural damage. (3) Oxidative stress pathways increase reactive oxygen species (ROS) and impair antioxidant defenses. In contrast, impaired neuroplasticity depends on insulin signaling, which triggers (4) PI3K/Akt and MAPK/ERK pathways. It should be noted that the activation of caspase-3 and Bcl-2 family proteins stimulate (5) mitochondrial apoptosis pathways in neurons. Besides, (6) the autophagy pathway dysregulates autophagic flux in neurons and impairs the clearance of protein aggregates, such as amyloid-beta. The foremost critical signaling pathway is elevated (7) tau phosphorylation, which has a reciprocal function by enacting glycogen synthase kinase 3β (GSK3β) and inhibiting protein phosphatase 2A (PP2A). Finally, PA can reduce (8) BDNF/TrkB signaling, which is involved in neuronal survival and plasticity.
Conclusion: As mentioned above, PA profoundly impacts AD-related crucial signaling pathways by disruption in neural metabolism, plasticity, and survival. The article, emphasizes the potential dietary and therapeutic implications based on the results. PA demonstrates stress level in ER, stimulates inflammatory pathways, increases oxidative stress, attenuates neuronal insulin signaling, activates apoptotic cascades, dysregulates autophagy, promotes tau hyperphosphorylation, and finally reduces BDNF/TrkB signaling. Limiting dietary intake of PA may therefore represent an accessible preventative strategy to reduce risk factors for sporadic AD. Furthermore, the development of targeted therapeutics to counteract the signaling disruptions triggered by PA in the brain may open new opportunities to halt neurodegeneration in the early stages of AD. Further research is still needed to fully elucidate the correlation between this prevalent dietary saturated fatty acid and the complex molecular pathways underpinning AD progression.