Identification of molecular targets and small drug candidates for Huntington's disease via bioinformatics and a network-based screening approach

被引：4

作者：

Hossain, Md Ridoy ^{[1
]}

Tareq, Md. Mohaimenul Islam ^{[1
]}

Biswas, Partha ^{[1
]}

Tauhida, Sadia Jannat ^{[1
]}

Bibi, Shabana ^{[2
,3
]}

Zilani, Md. Nazmul Hasan ^{[4
]}

Albadrani, Ghadeer M. ^{[5
]}

Al-Ghadi, Muath Q. ^{[6
]}

Abdel-Daim, Mohamed M. ^{[7
,8
]}

Hasan, Md. Nazmul ^{[1
]}

机构：

[1] Jashore Univ Sci & Technol, Dept Genet Engn & Biotechnol, Lab Pharmaceut Biotechnol & Bioinformat, Jashore, Bangladesh

[2] Shifa Tameer E Millat Univ, Dept Biosci, Islamabad, Pakistan

[3] Novel Global Community Educ Fdn, Dept Hlth Sci, Hebersham, NSW, Australia

[4] Jashore Univ Sci & Technol, Dept Pharm, Jessore, Bangladesh

[5] Princess Nourah Bint Abdulrahman Univ, Coll Sci, Dept Biol, Riyadh, Saudi Arabia

[6] King Saud Univ, Coll Sci, Dept Zool, Riyadh, Saudi Arabia

[7] Batterjee Med Coll, Dept Pharmaceut Sci, Pharm Program, Jeddah, Saudi Arabia

[8] Suez Canal Univ, Fac Vet Med, Pharmacol Dept, Ismailia, Egypt

来源：

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2024年 / 28卷 / 16期

关键词：

CAG (cytosine-adenine-guanine); degenerative; gene set enrichment analysis (GSEA); Huntington's disease; SET ENRICHMENT ANALYSIS; INTELLECTUAL DISABILITY; REGULATORY NETWORK; MECHANISMS; MUTATIONS; PATHWAY; CANCER; NEURODEGENERATION; DIFFERENTIATION; PROGRESSION;

D O I：

10.1111/jcmm.18588

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Huntington's disease (HD) is a gradually severe neurodegenerative ailment characterised by an increase of a specific trinucleotide repeat sequence (cytosine-adenine-guanine, CAG). It is passed down as a dominant characteristic that worsens over time, creating a significant risk. Despite being monogenetic, the underlying mechanisms as well as biomarkers remain poorly understood. Furthermore, early detection of HD is challenging, and the available diagnostic procedures have low precision and accuracy. The research was conducted to provide knowledge of the biomarkers, pathways and therapeutic targets involved in the molecular processes of HD using informatic based analysis and applying network-based systems biology approaches. The gene expression profile datasets GSE97100 and GSE74201 relevant to HD were studied. As a consequence, 46 differentially expressed genes (DEGs) were identified. 10 hub genes (TPM1, EIF2S3, CCN2, ACTN1, ACTG2, CCN1, CSRP1, EIF1AX, BEX2 and TCEAL5) were further differentiated in the protein-protein interaction (PPI) network. These hub genes were typically down-regulated. Additionally, DEGs-transcription factors (TFs) connections (e.g. GATA2, YY1 and FOXC1), DEG-microRNA (miRNA) interactions (e.g. hsa-miR-124-3p and has-miR-26b-5p) were also comprehensively forecast. Additionally, related gene ontology concepts (e.g. sequence-specific DNA binding and TF activity) connected to DEGs in HD were identified using gene set enrichment analysis (GSEA). Finally, in silico drug design was employed to find candidate drugs for the treatment HD, and while the possible modest therapeutic compounds (e.g. cortistatin A, 13,16-Epoxy-25-hydroxy-17-cheilanthen-19,25-olide, Hecogenin) against HD were expected. Consequently, the results from this study may give researchers useful resources for the experimental validation of Huntington's diagnosis and therapeutic approaches.

引用

页数：21

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