Neuroinflammation- molecular target based therapeutic approach

Chronic neuroinflammation has become a major concern due to its ability to propagate into multiple neurodegenerative disorders which severely reduce the life expectancy of the patients. Many molecular targets have been identified which include amyloid beta (Aβ) peptides and oligomers, protofibrils, tau proteins, MID1/ TRIM18, Beclin1 protein, Puma, NMDA receptors, RyanR2, 5-HT2B, α7nAChR, TLR4, ERRα, CysLT(1)R, PDGFβR, DRD1, β2-AR, caspases, calpain, cytochrome c, CDK5, p38-MAPK, BACE1, γ-secretase, 5-lipoxygenase, NADPH oxidase 2 and 4, JNK, MMPs, NLRP3, GSAP, PARP-1, PARG, TRPM2, H₂O₂, NO (excess), LTB4, LTD4, NF-κB (NF-kBp50/RelA dimers and NF-κB p65), TNF-α,IL-1β, IL-6, IL-10, ApoE2, ApoE4, Bax,Bcl-2, miR-9, miR-29, miR-29a/b-1, miR-101, miR-124, miR-107, miR-298, miR-149, miR-328, miR-34a-5p, miR-15b, miR-16, miR-125b-5p, miR-124, and miR-374b-5p, miR-181c-5p, linc00507, LncRNA 51A, LncRNA 17A, LncRNA BC200, LncRNA NDM29, LncRNA NEAT1, LncRNA EBF3-AS, LncRNA NAT-Rad18, LcRNA TUG1, LncRNA MALAT1, LncRNA WT1-AS, LncRNA MAGI2-AS3, XBP-1, SERCA, Na⁺/Ca²⁺exchanger, plasma-membrane Ca²⁺-ATPase, HSP27, mtHSP60/HSPD1-mtHSP10/HSPE1, HSPD1, HSPE1, HSP70, Hsp90, Sirt1, Sirt3, TIMP-123 (composite of TIMP-1, TIMP-2, and TIMP-3), TIMP-4, AChEI, BDNF. Identification of the molecular targets enabled the identification of phytoconstituents which could modulate majority of these molecular targets. A herbal formulation which is expected to alleviate neuroinflammation includes many phytoconstituents such as curcumin, (-)-epigallocatechin-3-gallate, baicalein, baicalin, resveratrol, cis-resveratrol, berberine, quercetin, apigenin, corosolic acid, ursolic acid, oleanolic acid, luteolin, albigenin, withanolide A, celastrol, gallotannin, nobotanin B, kaempferol, naringenin, rutin, withaferin A, crocetin, katsumain H, geranylgeranylacetone and huperzine. A compatibility study with different phytoconstituents will determine the suitability of the formulation.