Author ORCID Identifier

https://orcid.org/0000-0001-7251-8739

Date of Award

17-8-2025

Document Type

Thesis

School

School of Chemical & Biotechnology

Programme

Ph.D.-Doctoral of Philosophy

First Advisor

Dr.Shanker Jha

Second Advisor

Dr.Prakash Shankaran

Keywords

Class II Transactivator, Interactome Analysis, Ciita Interactors, Molecular Docking, Neuroinflammation

Abstract

Inflammation plays a significant role in maintaining homeostasis. Neuroinflammation is a chronic inflammatory response in the central nervous system (CNS), leading to brain or spinal cord dysfunction. To promote mental health, it is crucial to understand the regulation of neuroinflammation. Class II transactivator (CIITA) is a master-regulator of the major histocompatibility complex II (MHCII).

Modulation of CIITA has been suggested as a promising intervention for inflammatory conditions, including neurological disorders. However, there is limited knowledge about the role of CIITA and its interactors in inflammation. This study aimed to understand the role of CIITA in neuroinflammation and neurological disorders using in-silico tools.

Here, we 1) constructed a phylogenetic tree for CIITA, 2) predicted its structures using computational tools, 3) analyzed its interactome with neuroinflammatory genes, 4) studied differential expression of CIITA and its interactors in the zebrafish brain following peripherally induced inflammation and, 5) performed in-silico screening to identify small molecules that could bind to the predicted structure of CIITA. Phylogenetic analysis revealed that the closest orthologs for human CIITA (hCIITA) are in monkeys, orangutans, mice, rats, frogs, and zebrafish.

The interactome analysis predicted that CIITA might primarily interact with the IL4/IL13 and hippo signaling pathways during neuroinflammation. LPS-induced inflammation in zebrafish suggested a role for CIITA in chronic inflammation in the brain.

Finally, based on our in-silico drug screening, we propose five molecules (ZINC5154833, F5254-0161, Arteannuin B, Creatinine, and Natural2) that could target CIITA. These results will help us understand the possible molecular pathways by which CIITA could regulate neuroinflammation and brain homeostasis.

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Graphical Abstract