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- Identification of new targets of S-nitrosylation in neural stem cells by thiol redox proteomicsPublication . Santos, Ana Isabel; Lourenco, Ana S.; Simão, Sónia; Marques-da-Silva, Dorinda; Santos, Daniela F.; Carvalho, Ana Paula Onofre de; Pereira, Ana Catarina; Izquierdo-Álvarez, Alicia; Ramos, Elena; Morato, Esperanza; Marina, Anabel; Martínez-Ruiz, Antonio; Araújo, InêsNitric oxide (NO) is well established as a regulator of neurogenesis. NO increases the proliferation of neural stem cells (NSC), and is essential for hippocampal injury-induced neurogenesis following an excitotoxic lesion. One of the mechanisms underlying non-classical NO cell signaling is protein S-nitrosylation. This post-translational modification consists in the formation of a nitrosothiol group (R-SNO) in cysteine residues, which can promote formation of other oxidative modifications in those cysteine residues. S-nitrosylation can regulate many physiological processes, including neuronal plasticity and neurogenesis. In this work, we aimed to identify S-nitrosylation targets of NO that could participate in neurogenesis. In NSC, we identified a group of proteins oxidatively modified using complementary techniques of thiol redox proteomics. S-nitrosylation of some of these proteins was confirmed and validated in a seizure mouse model of hippocampal injury and in cultured hippocampal stem cells. The identified S-nitrosylated proteins are involved in the ERK/MAPK pathway and may be important targets of NO to enhance the proliferation of NSC.
- Nitric Oxide Regulates Neurogenesis in the Hippocampus following SeizuresPublication . Carreira, Bruno P.; Santos, Daniela F.; Santos, Ana Isabel; Carvalho, Caetana M.; Araújo, InêsHippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO). In these conditions, NO promotes proliferation of neural stem cells (NSC) in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA) induced seizuremouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.
- Oxidative stress and aging: synergies for age related diseasesPublication . Filipa Santos, Daniela; Simao, Sonia; Nóbrega, Clévio; Bragança, José; Castelo-Branco, Pedro; Pombinho de Araújo, Inês Maria; ALFA Score ConsortiumAging is characterized by a progressive decline in physiological function and underlies several disabilities, including the increased sensitivity of cells and tissues to undergo pathological oxidative stress. In recent years, efforts have been made to better understand the relationship between age and oxidative stress and further develop therapeutic strategies to minimize the impact of both events on age-related diseases. In this work, we review the impact of the oxidant and antioxidant systems during aging and disease development and discuss the crosstalk of oxidative stress and other aging processes, with a focus on studies conducted in elderly populations.
- Unraveling the potential of gasotransmitters as neurogenic and neuroprotective molecules: focus on Alzheimer's and Parkinson's diseases.Publication . Simao, Sonia; Filipa Santos, Daniela; Teixeira, Mariana; Agostinho, Rafaela R.; Rodrigues, Joana; Vitorino, Marta; Araújo, Inês M.Alzheimer's disease and Parkinson's disease are the two most prevalent neurodegenerative disorders worldwide, both characterized by progressive neuronal loss. Despite distinct pathophysiological features, they share cellular dysfunctions such as abnormal protein aggregation, oxidative stress, and neuroinflammation, research into which might be beneficial for developing novel therapeutic strategies that could tackle both conditions. This review highlights the emerging role of the gasotransmitters nitric oxide, carbon monoxide and hydrogen sulfide as modulators of adult neurogenesis and neuroprotection in Alzheimer's disease and Parkinson's disease. We have gathered recent evidence demonstrating that these endogenous gases exert anti-inflammatory, antioxidant, and anti-apoptotic effects, and, critically, promote neurogenesis - suggesting a dual neuroprotective and neuroregenerative therapeutic potential. The unique physicochemical features of these gasotransmitters, including their ability to cross the blood-brain barrier and diffuse rapidly throughout the neural tissue, further support their suitability as candidates for innovative neuroregenerative treatments. While clinical translation remains challenging, harnessing the neurogenic and neuroprotective actions of these gasotransmitters may offer transformative avenues for addressing the increasing burden of Alzheimer's disease and Parkinson's disease.