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Preclinical validation of a new hybrid molecule loaded in liposomes for melanom...

Pinho, Jacinta O.; Matias, Mariana; Marques, Vanda; Eleutério, Carla; Fernandes, Célia; Gano, Lurdes; Amaral, Joana D.; Mendes, Eduarda

The aggressiveness of melanoma and lack of effective therapies incite the discovery of novel strategies. Recently, a new dual acting hybrid molecule (HM), combining a triazene and a ʟ-tyrosine analogue, was synthesized. HM was designed to specifically be activated by tyrosinase, the enzyme involved in melanin biosynthesis and overexpressed in melanoma. HM displayed remarkable superior antiproliferative activity...


miR-335 targets LRRK2 and mitigates inflammation in Parkinson’s disease

Oliveira, Sara; Dionísio, Pedro A.; Gaspar, Maria Manuela; Correia Guedes, Leonor; Coelho, Miguel; Rosa, Mário Miguel; Ferreira, Joaquim J

Parkinson's disease (PD) is mainly driven by dopaminergic neuronal degeneration in the substantia nigra pars compacta accompanied by chronic neuroinflammation. Despite being mainly sporadic, approximately 10% of all cases are defined as heritable forms of PD, with mutations in the leucine-rich repeat kinase (LRRK2) gene being the most frequent known cause of familial PD. MicroRNAs (miRNAs or miRs), including mi...


Activation of necroptosis in human and experimental cholestasis

Afonso, Marta; Rodrigues, Pedro; Simão, André; Ofengeim, Dimitry; Carvalho, Tânia; Amaral, Joana D.; Gaspar, Maria Manuela; Cortez-Pinto, Helena

Cholestasis encompasses liver injury and inflammation. Necroptosis, a necrotic cell death pathway regulated by receptor-interacting protein (RIP) 3, may mediate cell death and inflammation in the liver. We aimed to investigate the role of necroptosis in mediating deleterious processes associated with cholestatic liver disease. Hallmarks of necroptosis were evaluated in liver biopsies of primary biliary cholangi...


Role of Nuclear Steroid Receptors in Apoptosis

Amaral, Joana D.; Sola, Susana; Steer, Clifford J.; Rodrigues, Cecilia M. P.

Nuclear steroid receptors (NSR) are ligand-activated transcription factors that play a key role in a variety of vital physiological phenomena including developmental or endocrine signaling, reproduction, and homeostasis. In addition, they are implicated in other important biological processes, such as apoptosis. Modulation of apoptosis by NSR is mostly associated with control of pro-apoptotic versus anti-apopto...


URSODEOXYCHOLIC ACID MODULATES THE UBIQUITIN-PROTEASOME DEGRADATION PATHWAY OF P53

Amaral, Joana D.; Castro, Rui E.; Sola, Susana; Rodrigues, Cecilia Maria M.


P53 is a specific molecular target of ursodeoxycholic acid in regulating apoptosis

Amaral, Joana D.; Castro, Rui E.; Sola, Susana; Steer, Clifford J.; Rodrigues, Cecilia Maria P.


Differential regulation of cyclin D1 and cell death by bile acids in primary ra...

Castro, Rui E.; Amaral, Joana D.; Sola, Susana; Kren, Betsy T.; Steer, Clifford J.; Rodrigues, Cecilia M. P.

Ursodeoxycholic ( UDCA) and tauroursodeoxycholic ( TUDCA) acids modulate apoptosis and regulate cell- cycle effectors, including cyclin D1. In contrast, deoxycholic acid ( DCA) induces cell death and cyclin D1. In this study, we explored the role of cycli


p53 is a key molecular target of ursodeoxycholic acid in regulating apoptosis

Amaral, Joana D.; Castro, Rui E.; Sola, Susana; Steer, Clifford J.; Rodrigues, Cecilia M. P.

p53 plays an important role in regulating expression of genes that mediate cell cycle progression and/or apoptosis. In addition, we have previously shown that the hydrophilic bile acid ursodeoxycholic acid (UDCA) prevents transforming growth factor beta 1-induced p53 stabilization and apoptosis in primary rat hepatocytes. Therefore, we hypothesized that p53 may represent an important target in bile acid-induced...


Functional modulation of nuclear steroid receptors by tauroursodeoxycholic acid...

Sola, Susana; Amaral, Joana D.; Borralho, Pedro M.; Ramalho, Rita M.; Castro, Rui E.; Aranha, Marcia M.; Steer, Cifford J.; Rodrigues, Cecilia M. P.

Tauroursodeoxycholic acid ( TUDCA) prevents amyloid beta-peptide (A beta)-induced neuronal apoptosis, by modulating both classical mitochondrial pathways and specific upstream targets. In addition, activation of nuclear steroid receptors (NSRs), such as t


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