9 documents found, page 1 of 1
Cleavage of the TrkB-FL receptor during epileptogenesis: insights from a kainic...
Ribeiro Rodrigues, Leonor; Fonseca-Gomes, João; Paulo, Sara L; Viais, Ricardo; Ribeiro, Filipa; Miranda-Lourenço, Catarina; Mouro, FranciscoBrain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and plasticity. In epilepsy, BDNF exhibits a dual role, exerting both antiepileptic and pro-epileptic effects. The cleavage of its main receptor, full-length tropomyosin-related kinase B (TrkB-FL), was suggested to occur in status epilepticus (SE) in vitro. Moreover, under excitotoxic conditions, TrkB-FL was found to b...
A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic ...
Fonseca-Gomes, João; Costa-Coelho, Tiago; Ferreira-Manso, Mafalda; Inteiro-Oliveira, Sara; Vaz, Sandra H.; Alemãn-Serrano, NunoIn Alzheimer's disease (AD), amyloid β (Aβ)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology seve...
Adenosinergic system and BDNF signaling changes as a cross-sectional feature of...
Miranda-Lourenço, Catarina; Rosa, Jéssica; Rei, Nádia; Belo, Rita F.; Lopes, Ana Luísa; Silva, Diogo; Vieira, Cátia; Magalhães-Cardoso, TeresaRett Syndrome is an X-linked neurodevelopmental disorder (RTT; OMIM#312750) associated to MECP2 mutations. MeCP2 dysfunction is seen as one cause for the deficiencies found in brain-derived neurotrophic factor (BDNF) signaling, since BDNF is one of the genes under MeCP2 jurisdiction. BDNF signaling is also dependent on the proper function of the adenosinergic system. Indeed, both BDNF signaling and the adenosin...
S327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early ...
Ferreira, Catarina B.; Marttinen, Mikael; Coelho, Joana E; Paldanius, Kaisa M.A.; Takalo, Mari; Mäkinen, Petra; Leppänen, LuukasAlzheimer's disease (AD) is the most common form of dementia, which is neuropathologically characterized by extracellular senile plaques containing amyloid-β and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Previous studies have suggested a role for septin (SEPTIN) protein family members in AD-associated cellular processes. Here, we elucidated the potential role of presynap...
Kyotorphin as a new pharmacological therapeutic strategy for Alzheimer’s Disease
Belo, Rita F.Kyotorphin (KTP, L-tyrosyl-L-arginine) is an endogenous dipeptide, described for the first time in 1979, as a potent analgesic molecule. Its naloxone-reversible opioid-like analgesic effect is indirectly mediated by the inducing the release of Met-enkephalin (Met-enk). It is currently accepted that KTP acts through a specific Gi-coupled receptor (KTPr), inducing Ca2+ influx in a phospholipase C-mediated process...
High-caloric diet Induces memory impairment and disrupts synaptic plasticity in...
Paulo, Sara L; Miranda-Lourenço, Catarina; Belo, Rita F.; Rodrigues, Rui S.; Fonseca-Gomes, João; Tanqueiro, Sara; Geraldes, Vera; Rocha, IsabelThe increasing consumption of sugar and fat seen over the last decades and the consequent overweight and obesity, were recently linked with a deleterious effect on cognition and synaptic function. A major question, which remains to be clarified, is whether obesity in the elderly is an additional risk factor for cognitive impairment. We aimed at unravelling the impact of a chronic high caloric diet (HCD) on memo...
Challenges of BDNF-based therapies : from common to rare diseases
Miranda-Lourenço, Catarina; Ribeiro Rodrigues, Leonor; Fonseca-Gomes, João; Tanqueiro, Sara; Belo, Rita F.; Ferreira, Catarina B.; Rei, NádiaNeurotrophins are a well-known family of neurotrophic factors that play an important role both in the central and peripheral nervous systems, where they modulate neuronal survival, development, function and plasticity. Brain-derived neurotrophic factor (BDNF) possesses diverse biological functions which are mediated by the activation of two main classes of receptors, the tropomyosin-related kinase (Trk) B and t...
Microglial Sirtuin 2 shapes long-term potentiation in hippocampal slices
Sa de Almeida, Joana; Vargas, Mariana; Fonseca-Gomes, João; Tanqueiro, Sara; Belo, Rita F.; Miranda-Lourenço, Catarina; Sebastião, Ana MMicroglial cells have emerged as crucial players in synaptic plasticity during development and adulthood, and also in neurodegenerative and neuroinflammatory conditions. Here we found that decreased levels of Sirtuin 2 (Sirt2) deacetylase in microglia affects hippocampal synaptic plasticity under inflammatory conditions. The results show that long-term potentiation (LTP) magnitude recorded from hippocampal slic...
The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced ...
Belo, Rita F.; Martins, Margarida L. F.; Shvachiy, Liana; Costa-Coelho, Tiago; de Almeida-Borlido, Carolina; Fonseca-Gomes, João; Neves, VeraKyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous dipeptide initially described to have analgesic properties. Recently, KTP was suggested to be an endogenous neuroprotective agent, namely for Alzheimer's disease (AD). In fact, KTP levels were shown to be decreased in the cerebrospinal fluid of patients with AD, and recent data showed that intracerebroventricular (i.c.v.) injection of KTP ameliorates memor...