Calcitonin gene‐related peptide (CGRP): A novel target for Alzheimer's disease

Abstract

Alzheimer's disease (AD) is leading cause of death among older characterized by neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and increased levels of amyloid-β (Aβ) peptides. Cholinergic treatment could be the best suitable physiological therapy for AD. Calcitonin gene-related peptide (CGRP) is a thirty-seven-amino acid regulatory neuropeptide resulting from different merging of the CGRP gene, which also includes adrenomedullin, amylin, calcitonin, intermedin, and calcitonin receptor-stimulating peptide. It is a proof for a CGRP receptor within nucleus accumbens of brain that is different from either the CGRP or CGRP receptor in which it demonstrates similar high-affinity binding for salmon calcitonin, CGRP, and amylin, a possession which is not shared by any extra CGRP receptors. Binding of CGRP to its receptor increases activated cAMP-dependent pkA and PI3 kinase, resulting in N-terminal fragments that are shown to exert complex inhibitory as well facilitator actions on nAChRs. Fragments such as CGRP1-4, CGRP1-5, and CGRP1-6 rapidly as well as reversibly improve agonist sensitivity of nAChRs without straight stimulating those receptors and produce the Ca -induced intracellular Ca mobilization. Renin-angiotensin-aldosterone system (RAAS)-activated angiotensin-type (AT4) receptor is also beneficial in AD. It has been suggested that exogenous administration of CGRP inhibits infiltration of macrophages and expression of various inflammatory mediators such as NFkB, IL-1b, TNF-α, iNOS, matrix metalloproteinase (MMP)-9, and cell adhesion molecules like intercellular adhesion molecule (ICAM)-1 which attenuates consequence of inflammation in AD. Donepezil, a ChEI, inhibits acetylcholinesterase and produces angiogenesis and neurogenesis, in the dentate gyrus of the hippocampus of WT mice after donepezil administration. However, none of the results discovered in CGRP-knockout mice and WT mice exposed to practical denervation. Therefore, selective agonists of CGRP receptors may become the potential candidates for treatment of AD.

Embelin impact on paraquat‐induced lung injury through suppressing oxidative stress, inflammatory cascade, and MAPK/NF‐κB signaling pathway

“…Evidence has been provided to recommend that MAPK might be contributing to the initiation of NF‐κB in the cytoplasm just as transactivation potential alteration in the nucleus. [ 43,44 ] As the outflow of these inflammatory mediators is regulated by NF‐κB, blocking transcriptional action of NF‐κB might be a significant focus for inflammatory response treatment. Our research propose that the inhibition of MAPK pathways by embelin might be a significant action underlying the weakening of paraquat‐prompted NF‐κB transcriptional action.…”

Wogonin ameliorate complete Freund's adjuvant induced rheumatoid arthritis via targeting NF‐κB/MAPK signaling pathway

“…The findings of the above research on wogonin obviously show its antiarthritis protective impacts. Because of its antioxidant characteristics, Wogonin is considered to produce its activity …”

Angiotensin II‐induced micro RNA‐21 culprit for non‐small‐cell lung adenocarcinoma

“…In fact, miR‐21 is upregulated in diverse tumors and plays a potential role in the angiogenesis of cancers (Zhao et al, ). These results indicate a role for miRNAs in lung tissues and plasma as molecular predictors of lung cancer development and aggressiveness and have theoretical and clinical implication for lung cancer management (Gupta et al, ; Rapalli et al, ; Singh et al, ).…”

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