Ial for DA neuron survival, like glial cell line-derived neurotrophic factor (GDNF), brain derived neurotrophic issue (BDNF), nerve growth aspect (NGF) and neuregulin (NRG), happen to be shown to activate the ERK5 pathway (Carlsson et al., 2011; Cavanaugh et al., 2001; Dickerson, 2010; Esparis-Ogando et al., 2002; Fox et al., 2001; Hayashi et al., 2001; Obara et al., 2009). In addition, a important role for ERK5 in NTF-induced survival of immature cortical, cerebellar, dorsal root ganglia, and superior cervical ganglion neurons has been reported (Finegan et al., 2009; Liu et al., 2003; Shalizi et al., 2003; Watson et al., 2001). Age-related declines in GDNF protein and GDNF and NRG receptors (GFR -1 and ErbB4, respectively) have already been noted in dopaminergic brain regions (Dickerson et al., 2009; Pruett and Salvatore, 2010; Yurek and Fletcher-Turner, 2001) and numerous NTFs are especially low in the SN of patients with Parkinson’s disease (Jenner and Olanow, 1998; Mogi et al., 1999; Siegel and Chauhan, 2000). These observations, as well as our current information, recommend that age-associated declines in nigral DA neurons (Eriksen et al., 2009; Fearnley and Lees, 1991; Fox et al., 2001; Morgan et al., 1987) and motor functions (Allen et al., 2011; Bennett et al., 1996; Boger et al., 2006; Irwin et al., 1994; Yue et al., 2012) could possibly be a consequence of decreased ERK5 activationNeurobiol Aging. Author manuscript; available in PMC 2015 March 01.Parmar et al.Pageresulting from reduced NTF signaling. It might also be noteworthy that inhibition in the ERK5 pathway has been shown to minimize GDNF mRNA and protein levels in some cells (Obara et al., 2011), suggesting a feedback loop in which MEK5-ERK5 signaling is further decreased. In conclusion, we present evidence for age-related modifications in total and phosphorylated ERK1, two, and 5 in DA-rich brain regions during normal aging. Additional, we have elucidated distinct roles of ERK1/2, and five in the basal survival of DA neurons and total cells in SN and VTA major cultures. As our data recommend that ERK5 activation is crucial for the survival of dopaminergic neurons, the use of NTFs that activate ERK5 may be a viable therapeutic selection to lower DA neuronal vulnerability and, thereby, lessen age-related motor deficits and the threat of parkinsonism.Formula of 1015610-39-5 NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThese studies have been funded by the National Institute of Aging (AG25848) plus the National Institute of Neurological Problems and Stroke (NS070825), Duquesne University, and the University of Pittsburgh.3-(tert-Butyl)cyclohexanone Chemscene S.PMID:23812309 L.W. was supported in component by summer student fellowship (PDFSFW- 1215) from the Parkinson’s Illness Foundation.
HIPPOKRATIA 2013, 17, 2:187-CASE REPORTBleomycin cardiotoxicity in the course of chemotherapy for an ovarian germ cell tumorDidagelos M, Boutis A, Diamantopoulos N, Sotiriadou M, Fotiou C1st Division of Clinical Oncology-Chemotherapy, Theagenio Cancer Hospital, Thessaloniki, GreeceAbstract Introduction: Platinum-based chemotherapeutic regimens, which includes BEP (bleomycin, etoposide, cisplatin) represent the regular of care, very first line therapy in non-epithelial ovarian tumours. Cardiovascular toxicity is a uncommon adverse impact of bleomycin. Case Report: A 41-year-old woman with ovarian granulosa tumor, treated with first line BEP chemotherapy experienced chest discomfort rapidly progressing to serious precordial discomfort during bleomycin infusion. The infusion was stopped and electrocar.
