8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Checking NEKs: Overcoming a Bottleneck in Human Diseases

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as the cell cycle, cell division, cilia formation, and the DNA damage response. The review of the literature points to the pivotal participation of NEKs in important human diseases, like different types of cancer, diabetes, ciliopathies and central nervous system related and inflammatory-related diseases. The different known regulatory molecular mechanisms specific to each NEK are also presented, relating to their involvement in different diseases. In addition, important information about NEKs remains to be elucidated and is highlighted in this review, showing the need for other studies and research regarding this kinase family. Therefore, the NEK family represents an important group of kinases with potential applications in the therapy of human diseases.

          Related collections

          Most cited references174

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors

          Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. However, its toll is higher in more developed countries. Reasons for vast differences in mortality rates of pancreatic cancer are not completely clear yet, but it may be due to lack of appropriate diagnosis, treatment and cataloging of cancer cases. Because patients seldom exhibit symptoms until an advanced stage of the disease, pancreatic cancer remains one of the most lethal malignant neoplasms that caused 432,242 new deaths in 2018 (GLOBOCAN 2018 estimates). Globally, 458,918 new cases of pancreatic cancer have been reported in 2018, and 355,317 new cases are estimated to occur until 2040. Despite advancements in the detection and management of pancreatic cancer, the 5-year survival rate still stands at 9% only. To date, the causes of pancreatic carcinoma are still insufficiently known, although certain risk factors have been identified, such as tobacco smoking, diabetes mellitus, obesity, dietary factors, alcohol abuse, age, ethnicity, family history and genetic factors, Helicobacter pylori infection, non-O blood group and chronic pancreatitis. In general population, screening of large groups is not considered useful to detect the disease at its early stage, although newer techniques and the screening of tightly targeted groups (especially of those with family history), are being evaluated. Primary prevention is considered of utmost importance. Up-to-date statistics on pancreatic cancer occurrence and outcome along with a better understanding of the etiology and identifying the causative risk factors are essential for the primary prevention of this disease.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The inflammasome: an integrated view.

            An inflammasome is a multiprotein complex that serves as a platform for caspase-1 activation and caspase-1-dependent proteolytic maturation and secretion of interleukin-1β (IL-1β). Though a number of inflammasomes have been described, the NLRP3 inflammasome is the most extensively studied but also the most elusive. It is unique in that it responds to numerous physically and chemically diverse stimuli. The potent proinflammatory and pyrogenic activities of IL-1β necessitate that inflammasome activity is tightly controlled. To this end, a priming step is first required to induce the expression of both NLRP3 and proIL-1β. This event renders the cell competent for NLRP3 inflammasome activation and IL-1β secretion, and it is highly regulated by negative feedback loops. Despite the wide array of NLRP3 activators, the actual triggering of NLRP3 is controlled by integration a comparatively small number of signals that are common to nearly all activators. Minimally, these include potassium efflux, elevated levels of reactive oxygen species (ROS), and, for certain activators, lysosomal destabilization. Further investigation of how these and potentially other as yet uncharacterized signals are integrated by the NLRP3 inflammasome and the relevance of these biochemical events in vivo should provide new insight into the mechanisms of host defense and autoinflammatory conditions. © 2011 John Wiley & Sons A/S.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component

              The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines including IL-1β and IL-18. We show that NLRP3 inflammasome activation is restricted to interphase of the cell cycle by NEK7, a serine/threonine kinase previously implicated in mitosis. NLRP3 inflammasome activation requires NEK7, which binds to the NLRP3 leucine-rich repeat domain in a kinase-independent manner downstream from the induction of mitochondrial ROS. This interaction is necessary for NLRP3-ASC complex formation, ASC oligomerization, and caspase-1 activation. NEK7 promotes the NLRP3-dependent cellular inflammatory response to intraperitoneal monosodium urate challenge, and the development of experimental autoimmune encephalitis in mice. Our findings suggest NEK7 serves as a cellular switch that enforces mutual exclusivity between the inflammasome response and cell division.
                Bookmark

                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                13 April 2020
                April 2020
                : 25
                : 8
                : 1778
                Affiliations
                [1 ]Instituto de Biologia, Departamento de Bioquímica e Biologia Tecidual, Universidade Estadual de Campinas, Campinas, São Paulo 13083-862, Brazil; andressa2401@ 123456gmail.com (A.P.d.O.); kazuo.bio@ 123456gmail.com (L.K.I.); isadora.bpavan@ 123456gmail.com (I.C.B.P.); fernandoriback@ 123456hotmail.com (F.R.S.); talitadinizmelo@ 123456yahoo.com.br (T.D.M.-H.)
                [2 ]Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas, Campinas, São Paulo 13083-871, Brazil
                [3 ]Laboratório Multidisciplinar em Alimentos e Saúde, Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, São Paulo 13484-350, Brazil; simabuco@ 123456gmail.com
                Author notes
                [* ]Correspondence: jorgkoba@ 123456unicamp.br ; Tel.: +55-19-3521-8143
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-1672-9686
                https://orcid.org/0000-0002-9419-0145
                Article
                molecules-25-01778
                10.3390/molecules25081778
                7221840
                32294979
                011b5cb8-f513-4799-8660-0df837a1f50a
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 March 2020
                : 09 April 2020
                Categories
                Review

                neks,cancer,disorders
                neks, cancer, disorders

                Comments

                Comment on this article