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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, Francisco

Brain-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, Nuno

In 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...


Selective modulation of epileptic tissue by an adenosine A3 receptor‐activating...

Ghosh, Anwesha; Ribeiro Rodrigues, Leonor; Ruffolo, Gabriele; Alfano, Veronica; Domingos, Cátia; Rei, Nádia; Tosh, Dilip K.; Rombo, Diogo M.

Background and purpose: Adenosine, through the A1 receptor (A1R), is an endogenous anticonvulsant. The development of adenosine receptor agonists as antiseizure medications has been hampered by their cardiac side effects. A moderately A1R-selective agonist, MRS5474, has been reported to suppress seizures without considerable cardiac action. Hypothesizing that this drug could act through other than A1R and/or th...


Sustained hippocampal neural plasticity questions the reproducibility of an amy...

Paulo, Sara L; Ribeiro Rodrigues, Leonor; Rodrigues, Rui S.; Mateus, Joana; Fonseca-Gomes, João; Soares, Rita; Diógenes, Maria José; Solá, Susana

Background: The use of Alzheimer's disease (AD) models obtained by intracerebral infusion of amyloid-β (Aβ) has been increasingly reported in recent years. Nonetheless, these models may present important challenges. Objective: We have focused on canonical mechanisms of hippocampal-related neural plasticity to characterize a rat model obtained by an intracerebroventricular (icv) injection of soluble amyloid-β42 ...


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, Nádia

Neurotrophins 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...


Neural stem cells and cannabinoids in the spotlight as potential therapy for ep...

Lourenço, Diogo M.; Ribeiro Rodrigues, Leonor; Sebastião, Ana M; Diógenes, Maria José; Xapelli, Sara

Epilepsy is one of the most common brain diseases worldwide, having a huge burden in society. The main hallmark of epilepsy is the occurrence of spontaneous recurrent seizures, having a tremendous impact on the lives of the patients and of their relatives. Currently, the therapeutic strategies are mostly based on the use of antiepileptic drugs, and because several types of epilepsies are of unknown origin, a hi...


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