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Molecular Crossfires between Inflammasome Signalling and Dietary Small Molecule Inhibitors in Neurodegenerative Diseases: Implications for Medical Nutrition Therapy

DOI : https://doi.org/10.36349/easjbg.2024.v06i04.002
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Neurodegenerative disorders are a range of debilitating conditions that manifest due to the progressive loss of neuronal cells in specific brain regions. Current therapeutic options are less than adequate in many respects. Protein misfolding and aggregation are hallmarks of the most common neurodegenerative disorders. Consequently, they elicit cellular homeostasis disruption, synaptic connection loss, and subsequent cellular apoptosis. In recent years, research has increasingly linked dysregulated inflammatory responses mediated by the inflammasome complex to several neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, Epilepsy, Huntington’s disease, Autism, stroke etc. The inflammasome is a cytosolic multiprotein complex that is essential for innate immunity. Microglia are the primary cells expressing inflammasomes in the central nervous system, although astrocytes, neurons, and infiltrating myeloid cells can also express and activate inflammasomes. Regrettably, dysregulated inflammasome signaling upregulates the release of pro-inflammatory cytokines, as well as activating caspase-1. This process contributes to the continuation of neuroinflammation and subsequent damage to neurons. In this review of existing literatures, we collated empirical evidences about various inflammasome signaling pathways in selected neurological disorders. Majorly, we emphasised their influence on the advancement of diseases and neuronal cell death. Available empirical data showed that dietary small molecule inhibitors offer multi-targeted interactions to inhibit inflammasome signalling and upstream neuroinflammation. Notably, the baseline mechanisms involve suppression of free radicals, downregulating NF-κB and NLRP3 oligomerization, activating anti-inflammatory pathways, reducing ER stress, and modulating the Nrf2-ARE pathway. This shows promise for developing innovative medical nutrition therapies for various neurological conditions.

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Dr. Afroza Begum

Lecturer, Dept. of Pharmacology and Therapeutics, Shaheed Monsur Ali Medical College & Hospital, Uttara, Dhaka-1230, Bangladesh

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