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Natural Products Attenuating Biosynthesis, Processing, and Activity of Ras Oncoproteins: State of the Art and Future Perspectives.

ABSTRACT: RAS genes encode signaling proteins, which, in mammalian cells, act as molecular switches regulating critical cellular processes as proliferation, growth, differentiation, survival, motility, and metabolism in response to specific stimuli. Deregulation of Ras functions has a high impact on human health: gain-of-function point mutations in RAS genes are found in some developmental disorders and thirty percent of all human cancers, including the deadliest. For this reason, the pathogenic Ras variants represent important clinical targets against which to develop novel, effective, and possibly selective pharmacological inhibitors. Natural products represent a virtually unlimited resource of structurally different compounds from which one could draw on for this purpose, given the improvements in isolation and screening of active molecules from complex sources. After a summary of Ras proteins molecular and regulatory features and Ras-dependent pathways relevant for drug development, we point out the most promising inhibitory approaches, the known druggable sites of wild-type and oncogenic Ras mutants, and describe the known natural compounds capable of attenuating Ras signaling. Finally, we highlight critical issues and perspectives for the future selection of potential Ras inhibitors from natural sources.

SUBMITTER: Tisi R

PROVIDER: S-EPMC7698260 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Natural Products Attenuating Biosynthesis, Processing, and Activity of Ras Oncoproteins: State of the Art and Future Perspectives.

Tisi Renata R Gaponenko Vadim V Vanoni Marco M Sacco Elena E

Biomolecules 20201110 11

<i>RAS</i> genes encode signaling proteins, which, in mammalian cells, act as molecular switches regulating critical cellular processes as proliferation, growth, differentiation, survival, motility, and metabolism in response to specific stimuli. Deregulation of Ras functions has a high impact on human health: gain-of-function point mutations in <i>RAS</i> genes are found in some developmental disorders and thirty percent of all human cancers, including the deadliest. For this reason, the pathog ...[more]

PMID: 33182807

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Project description:Current research suggests that the management of neurological diseases, both in adults and children, requires an ever increasing commitment of resources for the national healthcare system (NHS). In Italy, due to the aging of the population, increase in chronicity and morbidity of pathologies, and presence of islands and rural areas, health needs to be supported by innovative technologies. Telemedicine is a method of providing healthcare services at distance, remotely connecting health professionals and patients (or two professionals). In Italy, telemedicine is under development, and the NHS has not yet exploited and independently developed all the possibilities that telemedicine offers. Tele-rehabilitation consists in the use of information and communication technologies for the remote support of rehabilitation services. By allowing “home care,” it represents a valid support during the home rehabilitation process. This review is aimed at evaluating the role of telerehabilitation in Italy, with regard to the motor and cognitive rehabilitation programs applied to neurological pathologies, in both pediatric and adult patients. We screened the studies published between 2010 and 2019 on PubMed, Scopus, Cochrane, and Web of Sciences databases. Using the PICO model, the search combined the terms “telerehabilitation”; “neurological disorders”; “neurodegenerative disease,” “motor telerehabilitation”; “cognitive rehabilitation.” This review showed that telerehabilitation is a promising healthcare tool, as it guarantees continuity of care over time (after discharge) and in space (from hospital to patient's home), especially in patients with stroke. Furthermore, it allows to increase the frequency and intensity of rehabilitation programs, provide individualized rehabilitation treatment in comfortable and familiar environment for patient, monitor and evaluate patients' needs and progress, stimulate patient motivation and achieve better patient satisfaction, verify the results achieved by the patients, and potentially reduce the service costs. Unfortunately, almost all neurorehabilitation studies are characterized by small samples and wide variability of results, and would benefit from standardized procedures, aims and targets. Future telerehabilitation trials should include cost-effectiveness analysis associated with clinical outcomes to better assess the validity of this promising tool.

Dataset Information

Natural Products Attenuating Biosynthesis, Processing, and Activity of Ras Oncoproteins: State of the Art and Future Perspectives.

Publications

Natural Products Attenuating Biosynthesis, Processing, and Activity of Ras Oncoproteins: State of the Art and Future Perspectives.

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