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Abstract: Alzheimer's disease (AD), the most common serious and disability issue with a significant economic impact on our society. Despite significant improvements in an etiology, diagnosis, and therapy, its underlying causes are still unknown, reliable biomarkers are not clearly defined, and current pharmaceutical therapies are not cost-effective. Effective care of AD and other dementia types are critical in patients for their healthy lifespan. Over the last two decades, developments in pathogenesis have piqued the interest of the scientific community in the development of new pharmacological treatments that target recognized disease targets. Pharmacological therapy has been recently ascribed to 10 - 20% of the direct expenses of AD. Less than 20% of Alzheimer's patients respond somewhat to standard medicines with questionable cost-effectiveness (donepezil, galantamine, memantine and rivastigmine). Therefore, currently known treatment approaches address the condition indirectly, as acetyl cholinesterase related inhibitors and the N-methyl d-aspartate as receptor and as antagonists have little effect on the sickness. Novel targets and specific small molecules must also be found in order to be useful in the therapy of AD. This chapter considers a wide range targets for Alzheimer's disease and current advances in the discovery of disease inhibitors. And also brief in-silico studies were highlighted and included to know how the theoretical lead is achievable in AD medication discovery.

Maintaining genomic stability is inevitable for organism survival and it is challenged by mutagenic agents, which include ultraviolet (UV) radiation. Whenever DNA damage occurs, it is sensed by DNA-repairing proteins and thereby performing the DNA-repair mechanism. Specifically, in response to DNA damage, H2AX is a key protein involved in initiating the DNA-repair processes. In this present study, we investigate the effect of UV-C on earthworm, Perionyx excavatus and analyzed the DNA-damage response. Briefly, we expose the worms to different doses of UV-C and find that worms are highly sensitive to UV-C. As a primary response, earthworms produce coelomic fluid followed by autotomy. However, tissue inflammation followed by death is observed when we expose worm to increased doses of UV-C. In particular, UV-C promotes damages in skin layers and on the contrary, it mediates the chloragogen and epithelial outgrowth in intestinal tissues. Furthermore, UV-C promotes DNA damages followed by upregulation of H2AX on dose-dependent manner. Our finding confirms DNA damage caused by UV-C is directly proportional to the expression of H2AX. In short, we conclude that H2AX is present in the invertebrate earthworm, which plays an evolutionarily conserved role in DNA damage event as like that in higher animals.

Maintaining genomic stability is inevitable for organism survival and it is challenged by mutagenic agents, which include ultraviolet (UV) radiation. Whenever DNA damage occurs, it is sensed by DNA-repairing proteins and thereby performing the DNA-repair mechanism. Specifically, in response to DNA damage, H2AX is a key protein involved in initiating the DNA-repair processes. In this present study, we investigate the effect of UV-C on earthworm, Perionyx excavatus and analyzed the DNA-damage response. Briefly, we expose the worms to different doses of UV-C and find that worms are highly sensitive to UV-C. As a primary response, earthworms produce coelomic fluid followed by autotomy. However, tissue inflammation followed by death is observed when we expose worm to increased doses of UV-C. In particular, UV-C promotes damages in skin layers and on the contrary, it mediates the chloragogen and epithelial outgrowth in intestinal tissues. Furthermore, UV-C promotes DNA damages followed by upregulation of H2AX on dose-dependent manner. Our finding confirms DNA damage caused by UV-C is directly proportional to the expression of H2AX. In short, we conclude that H2AX is present in the invertebrate earthworm, which plays an evolutionarily conserved role in DNA damage event as like that in higher animals.