cardiovascular-agents and Neurodegenerative-Diseases

The preventive effects of olive oil against different diseases have been attributed to its high phenolic compound content. The objective of this study was to examine available scientific evidence on the beneficial effects against chronic diseases of olive oil phenolic compounds.. This article examines recently published data on olive oil phenolic compounds and their potential benefits in the prevention of cardiovascular disease, cancer, neurodegenerative disease, and osteoporosis.. The antioxidant, anti-proliferative, pro-apoptotic, and anti-inflammatory activities of olive oil phenolic compounds have preventive effects against heart disease and cancer. These compounds also exert neuroprotective and neuromodulator effects against neurodegenerative disease, inhibiting the development of amyloid plaques. Finally, they are known to protect against osteoporosis, favoring bone regeneration.. Dietary intake of olive oil can be recommended by healthcare professionals as an important source of phenolic compounds that play a role in the prevention of chronic disease and the consequent improvement in quality of life.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Bone Density Conservation Agents; Cardiovascular Agents; Cardiovascular Diseases; Diet, Healthy; Humans; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Olive Oil; Osteoporosis; Phenols; Protective Factors; Risk Factors

Multi-target and combinatorial therapies have been focused for the past several decades. These approaches achieved considerable therapeutic efficacy by modulating the activities of the targets in complex diseases such as HIV-1 infection, cancer and diabetes disease. Most of the diseases cannot be treated efficiently in terms of single gene target, because it involves the cessation of the coordinated function of distinct gene groups. Most of the cellular components work efficiently by interacting with other cellular components and all these interactions together represent interactome. This interconnectivity shows that a defect in a single gene may not be restricted to the gene product itself, but may spread along the network. So, drug development must be based on the network-based perspective of disease mechanisms. Many systematic diseases like neurodegenerative disorders, cancer and cardiovascular cannot be treated efficiently by the single gene target strategy because these diseases involve the complex biological machinery. In clinical trials, many mono-therapies have been found to be less effective. In mono-therapies, the long term treatment, for the systematic diseases make the diseases able to acquired resistance because of the disease nature of the natural evolution of feedback loop and pathway redundancy. Multi-target drugs might be more efficient. Multi-target therapeutics might be less vulnerable because of the inability of the biological system to resist multiple actions. In this study, we will overview the recent advances in the development of methodologies for the identification of drug target interaction and its application in the poly-pharmacology profile of the drug.

Topics: Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; Drug Evaluation, Preclinical; Gene Regulatory Networks; Humans; Molecular Targeted Therapy; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Polypharmacology

This review summarizes recent progress in understanding the role of p53-upregulated mediator of apoptosis (PUMA) in molecular pathways with respect to its potential therapeutic applications. Particular emphasis is given to the PUMA´s role in ionizing radiation-induced signalling as radiotoxicity of normal tissue is mediated mostly via apoptosis. PUMA and its p53-dependent and p53- independent induction are described and potential use as a new target for the development of radioprotective agents is suggested. Further implications, including targeting PUMA to prevent and treat cardiovascular and neurodegenerative diseases, are also discussed together with an overview of other therapeutic applications. Finally, basic chemical structures for the development of novel PUMA modulators such as pifithrine derivatives, kinase inhibitors or modulators of Bcl-2 protein family are described.

Topics: Apoptosis; Apoptosis Regulatory Proteins; Cardiovascular Agents; Cardiovascular Diseases; DNA Damage; Humans; Molecular Targeted Therapy; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Protein Binding; Proto-Oncogene Proteins; Radiation Injuries; Radiation Tolerance; Radiation-Protective Agents; Signal Transduction; Tumor Suppressor Protein p53

Resistance to anticancer drugs is often related to deficient cell death execution pathways in cancer cells. Apoptosis, which denotes a form of cell death executed by caspases, was traditionally considered as the only physiological and programmed form of cell death. However, recent evidence indicates that programmed cell death (PCD) can occur in complete absence of caspase activation. Indeed, a large number of caspase-independent models are now defined and a key protein implicated in this type of PCD, apoptosis-inducing factor (AIF), has been identified. AIF is a mitochondrial protein with two faces looking in opposite life/death directions. Recently, the identification of five different isoforms allowed a better characterization of AIFs life/mitochondrial versus death/nuclear functions, as well as definition of its pro-apoptotic region and some of its nuclear partners. Importantly, much work on caspase-independent PCD has revealed that AIF participates in more PCD systems than initially thought. A wider molecular knowledge of AIF, and of the caspase-independent PCDs in which it is involved, are key to provide new insights into the role of PCD. There is no doubt that these insights will lead to the development of more selective and efficient drugs against cancer, degenerative diseases, and other pathological disorders implicating AIF.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Apoptosis; Apoptosis Inducing Factor; Cardiovascular Agents; Caspases; Cell Nucleus; Drug Resistance, Neoplasm; Enzyme Activation; Humans; Ischemia; Mitochondria; Models, Molecular; Molecular Sequence Data; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Protein Conformation; Protein Isoforms