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Cholesterol redistribution triggered by CYP46A1 gene therapy improves major hal...

Nunes, Maria João; Carvalho, Andreia N.; Reis, Joana; Costa, Daniela; Moutinho, Miguel; Mateus, Joana; Mendes de Almeida, Rita; Brito, Sara

Cholesterol 24-hydroxylase (CYP46A1) is an exclusively neuronal cytochrome P450 enzyme responsible for converting cholesterol into 24S-hydroxycholesterol, which serves as the primary pathway for eliminating cholesterol in the brain. We and others have shown that increased activity of CYP46A1 leads to reduced levels of cholesterol and has a positive effect on cognition. Therefore, we hypothesized that CYP46A1 co...


Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflamm...

Mendes, Mariana Oliveira; Rosa, Alexandra Isabel; Carvalho, Andreia Neves; Nunes, Maria João; Dionísio, Pedro; Rodrigues, Elsa; Costa, Daniela

Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and by the presence of intracellular inclusions, known as Lewy bodies. Despite SNpc being considered the primary affected region in PD, the neuropathological features are confined solely to the nigro-striatal axis. With disease progres...


Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson...

Rosa, Alexandra Isabel; Silva, Sara Carina Duarte; Silva-Fernandes, Anabela; Nunes, Maria João; Carvalho, Andreia Neves; Rodrigues, Elsa

Parkinson's disease (PD) is characterized by severe motor symptoms, and currently there is no treatment that retards disease progression or reverses damage prior to the time of clinical diagnosis. Tauroursodeoxycholic acid (TUDCA) is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD; however, its effect in PD motor symptoms has never been addressed. In the present work...


GSTpi Expression in MPTP-Induced Dopaminergic Neurodegeneration of C57BL/6 Mous...

Castro-Caldas, Margarida; Carvalho, Andreia Neves; Peixeiro, Isabel; Rodrigues, Elsa; Lechner, Maria Celeste; Gama, Maria Joao

MPTP-induced dopaminergic neurotoxicity involves major biochemical processes such as oxidative stress and impaired energy metabolism, leading to a significant reduction in the number of nigrostriatal dopaminergic neurons. Glutathione S-transferase pi (GSTpi) is a phase II detoxifying enzyme that provides protection of cells from injury by toxic chemicals and products of oxidative stress. In humans, polymorphism...


Glutathione S-transferase pi regulates UV-induced JNK signaling in SH-SY5Y neur...

Castro-Caldas, Margarida; Milagre, Ines; Rodrigues, Elsa; Gama, Maria Joao

Activation of c-Jun N-terminal kinase (JNK) signaling pathway is a key event in apoptosis. The cellular mechanisms underlying the control of JNK catalytic activity before and immediately after stress in neuronal cells are still not completely understood. Under resting conditions the basal activity of JNK is low, since JNK is kept inactive by the presence of one or more endogenous repressors, including glutathio...


17beta-estradiol promotes the synthesis and the secretion of annexin I in the C...

Castro-Caldas, Margarida; Duarte, Carlos B.; Carvalho, Arsélio P.; Lopes, M. Celeste

AIMS: Annexin I (ANXA1), a 37kDa member of the annexin family of Ca2+-binding and phospholipid-binding proteins, is particularly abundant in various populations of peripheral blood leukocytes. Since this protein modulates the anti-inflammatory actions of the steroid hormones, the purpose of this study was to investigate the effects of the female sex steroid hormone, 17beta-estradiol (E2beta), on the synthesis a...


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