Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities.

The skin containing melanin pigment acts as a protective barrier and counteracts the UVR and other environmental stressors to maintain or restore disrupted cutaneous homeostasis. The production of melanin pigment is dependent on tyrosine levels. L-tyrosine and L-dihydroxyphenylalanine (L-DOPA) can serve both as a substrates and intermediates of melanin synthetic pathway and as inducers and positive regulators of melanogenesis. The biosynthesis of melanin is stimulated upon exposure to UVR, which can also stimulate local production of hormonal factors, which can stimulate melanoma development by altering the chemical properties of eu- and pheomelanin. The process of melanogenesis can be altered by several pathways. One involves activation of POMC, with the production of POMC peptides including MSH and ACTH, which increase intracellular cAMP levels, which activates the MITF, and helps to stimulate tyrosinase (TYR) expression and activity. Defects in OCA1 to 4 affects melanogenic activity via posttranslational modifications resulting in proteasomal degradation and reducing pigmentation. Further, altering, the MITF factor, helps to regulate the expression of MRGE in melanoma, and helps to increase the TYR glycosylation in ER. CRH stimulates POMC peptides that regulate melanogenesis and also by itself can stimulate melanogenesis. The POMC, P53, ACTH, MSH, MC1R, MITF, and 6-BH4 are found to be important regulators for pigmentation. Melanogenesis can affect melanoma behaviour and inhibit immune responses. Therefore, we reviewed natural products that would alter melanin production. Our special focus was on targeting melanin synthesis and TYR enzyme activity to inhibit melanogenesis as an adjuvant therapy of melanotic melanoma. Furthermore, this review also outlines the current updated pharmacological studies targeting the TYR enzyme from natural sources and its consequential effects on melanin production.

Caenorhabditis elegans as a possible model to screen anti-Alzheimer's therapeutics.

Alzheimer's disease (AD) is regarded as one of the significant health burdens, as the prevalence is raising worldwide and gradually reaching to epidemic proportions. Consequently, a number of scientific investigations have been initiated to derive therapeutics to combat AD with a concurrent advancement in pharmacological methods and experimental models. Whilst, the available experimental pharmacological approaches both in vivo and in vitro led to the development of AD therapeutics, the precise manner by which experimental models mimic either one or more biomarkers of human pathology of AD is gaining scientific attentions. Caenorhabditis elegans (C. elegans) has been regarded as an emerging model for various reasons, including its high similarities with the biomarkers of human AD. Our review supports the versatile nature of C. elegans and collates that it is a well-suited model to elucidate various molecular mechanisms by which AD therapeutics elicit their pharmacological effects. It is apparent that C. elegans is capable of establishing the pathological processes that links the endoplasmic reticulum and mitochondria dysfunctions in AD, exploring novel molecular cascades of AD pathogenesis and underpinning causal and consequential changes in the associated proteins and genes. In summary, C. elegans is a unique and feasible model for the screening of anti-Alzheimer's therapeutics and has the potential for further scientific exploration.