2. Academic Validation
  3. Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain

Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain

  • Int J Mol Sci. 2022 Oct 30;23(21):13224. doi: 10.3390/ijms232113224.
Sharad Singh 1,  Ibrahim Ahmed Shaikh 2,  Sunil S More 1,  Mater H Mahnashi 3,  Hailah M Almohaimeed 4,  Mohamed El-Sherbiny 5 6,  Mohammed M Ghoneim 7 8,  Ahmad Umar 9 10,  Harshit Kumar Soni 11,  Himanshu Agrawal 12,  Basheer Ahmed Mannasaheb 8,  Aejaz Abdullatif Khan 13,  Uday M Muddapur 14,  S M Shakeel Iqubal 13
Affiliations

Affiliations

  • 1 School of Basic and Applied Sciences, Dayananda Sagar University, Bangalore 560111, Karnataka, India.
  • 2 Department of Pharmacology, College of Pharmacy, Najran University, P.O. Box 1988, Najran 66462, Saudi Arabia.
  • 3 Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, P.O. Box 1988, Najran 66462, Saudi Arabia.
  • 4 Department of Basic Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
  • 5 Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia.
  • 6 Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
  • 7 Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
  • 8 Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Dariyah, P.O. Box 71666, Riyadh 13713, Saudi Arabia.
  • 9 Department of Chemistry, Faculty of Science and Arts, Najran University, P.O. Box 1988, Najran 11001, Saudi Arabia.
  • 10 Promising Centre for Sensors and Electronic Devices (PCSED), Najran University, P.O. Box 1988, Najran 11001, Saudi Arabia.
  • 11 Department of Zoology, Government Science College, Pandhurna 480334, Madhya Pradesh, India.
  • 12 Jubilant Biosys Limited (Discovery Biology), Bangalore 560022, Karnataka, India.
  • 13 Department of General Science, Ibn Sina National College for Medical Studies, P.O. Box 31906, Jeddah 21418, Saudi Arabia.
  • 14 Department of Biotechnology, KLE Technological University, BVB Campus, Hubballi 580031, Karnataka, India.
PMID: 36362011 DOI: 10.3390/ijms232113224
Abstract

Manganese neurotoxicity has been reported to cause a neurodegenerative disease known as parkinsonism. Previous reports have shown that the expression of the KH-type splicing regulatory protein (KHSRP), a nucleic acid-binding protein, and NLRP3 is increased upon Mn exposure. However, the relation between these two during Mn toxicity has not been fully deduced. The mouse neuroblastoma (N2a) and SD rats are treated with LPS and MnCl2 to evaluate the expression of KHSRP and NLRP3. Further, the effect of the NLRP3 Inhibitor MCC950 is checked on the expression of NLRP3, KHSRP and pro-inflammatory markers (TNFα, IL-18 and IL-1β) as well as the Caspase-1 enzyme. Our results demonstrated an increment in NLRP3 and KHSRP expression post-MnCl2 exposure in N2a cells and rat brain, while on the Other hand with LPS exposure only NLRP3 expression levels were elevated and KHSRP was found to be unaffected. An increased expression of KHSRP, NLRP3, pro-inflammatory markers and the Caspase-1 enzyme was observed to be inhibited with MCC950 treatment in MnCl2-exposed cells and rats. Manganese exposure induces NLRP3 and KHSRP expression to induce neuroinflammation, suggesting a correlation between both which functions in toxicity-related pathways. Furthermore, MCC950 treatment reversed the role of KHSRP from anti-inflammatory to pro-inflammatory.

Keywords

KHSRP; N2a cells; Parkinson’s; manganese neurotoxicity; neuroinflammation.

Figures
Products