Postulating the possible cellular signalling mechanisms of antibody drug conjugates in Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in the world. Although the basic pathology of the disease is elucidated, it is difficult to restore or prevent the worsening of neurodegeneration and its symptoms. Antibody and small molecule-based approaches have been studied and are in study individually, but a combined approach like conjugation has not been performed to date. The conjugation between antibodies and drugs which are already used for Alzheimer's treatment or developed specifically for this purpose may have better efficacy and dual action in mitigating Alzheimer's disease. A probable mechanism for antibody-drug conjugates in Alzheimer's disease is discussed in the present review.

Exploring the Mitochondrial Apoptotic Cell Death Landscape and Associated Components Serving as Molecular Targets, Primarily for Synthetic and Natural Drugs Targeting Oncology Therapeutics.

The role of mitochondria in the apoptosis signaling cell death pathway is regulated by extrinsic and intrinsic pathway, encompassing multiple components like the Bcl-2 family of proteins, death receptors, caspases, Smac/DIABLO, IAPs, Omi/HtrA2 and cytochrome c. These entities serve as effective molecular targets for numerous drugs targeting mitochondrial apoptotic pathways, mainly emphasizing oncology therapeutics. Defective apoptosis is an acquired hallmark of cancer cells, which promotes the establishment of apoptosis-targeting anti-cancer drugs in cancer treatment. The review provides an overview of the Bcl-2 inhibiting, IAPs antagonizing, caspase inhibiting and BH3 mimicking actions, mediated by anti-cancer drugs, rendering beneficial outcomes in different forms of cancer. The authors elaborate on the significance of synthetic and natural agents, targeting the mitochondrial apoptotic pathway, in ameliorating tumor cell growth in the body, and the specificity and effectiveness of these agents, motivating the researchers to explore mitochondrial apoptosis targeting of anti-tumor drugs of both herbal and synthetic origin. Thus, the review aims to predict this dynamic approach in oncology, simultaneously highlighting the challenges and future prospects, providing an opportunity to the experts to "go over with a fine tooth comb" in understanding this "programmed cell death pathway", and establishing reliability and accuracy of this therapeutic paradigm in the upcoming future.

Understanding the possible role of endocannabinoid system in obesity.

BACKGROUND: Maintenance of weight is essential for sustenance, well-being and to endorse prolonged life. The prevalence of obesity is increasing at an alarming rate globally, due to modern lifestyle and dietary habits. Endocannabinoids are fatty acid derivatives and numerous studies are carried out which focuses and targets their relationship with obesity, via multiple signals which have been recently known for exerting crucial role in regulating energy balance. PURPOSE: This article aims at examining the prospects of endocannabinoids in obesity via directing the role of ECs in stimulating hunger. RESULT: In last few years, irregular stimulation of endocannabinoid system has been suggested as a chief element in the progression of obesity-associated metabolic complications. Certainly, this cascade system comprises of cannabinoid type1 and 2 receptors (CB1R and CB2R) along with their endogenous lipid ligands which are responsible for enhanced feeding behavior as well as lipid metabolism. Significantly, inhibiting CB1R activity might reduce metabolic abnormality linked with obesity. CONCLUSION: Conclusion withdrawn on the basis of supporting scientific data and evidences report that the blockade of cannabinoids can serve as a therapeutic potential for treatment of obesity. Future prospective aims at assessing molecular pathways which contributes towards ECS, elicited weight control and to evaluate how these mechanisms are presently relocated into the production of novel cannabinoid drugs exhibiting enriched care.

The endocannabinoid signaling pathway as an emerging target in pharmacotherapy, earmarking mitigation of destructive events in rheumatoid arthritis.

Rheumatoid arthritis is an inflammatory autoimmune disease, characterized by synovial proliferation, destruction to articular cartilage and severe pain. The cannabinoids obtained from Cannabis sativa exhibited their actions via cannabinoid-1 and -2 receptors, which also provides a platform for endocannabinoids to act. The endocannabinoid system comprises endocannabinoid molecules involved in signaling processes, along with G-protein coupled receptors and enzymes associated with ligand biosynthesis, activation and degradation. The action of endocannabinoid system in immune system regulation, via primary CB2 activation, followed by inhibition of production of pro-inflammatory cytokines, auto-antibodies and MMPs, FLSs proliferation and T-cell mediated immune response, are elaborated as potential therapeutic regimes in rheumatoid arthritis. The involvement of endocannabinoid system in immune cells like, B cells, T cells and macrophages, as well as regulatory actions on sensory noniceptors to ameliorate pain is significantly highlighted in the review, elaborating the actions of endocannabinoid signaling in mitigating the disease events. The review also focuses on enhancement of endocannabinoid tone, either by inhibiting the degradation enzymes, like FAAH, MAGL, COX, CytP450, LOX, etc. or by retarding cellular uptake processes. Moreover, the review portrays the optimizing role of endocannabinoid system, in abbreviating the symptoms and complications of rheumatoid arthritis in patients and mitigating inflammation, pain and immune mediated effects significantly.