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Glycation modulates glutamatergic signaling and exacerbates Parkinson’s disease...
Chegão, Ana; Guarda, Mariana; Alexandre, Bruno M.; Shvachiy, Liana; Temido Ferreira, Mariana; Marques-Morgado, Inês; Fernandes Gomes, BárbaraAlpha-synuclein (aSyn) is a central player in the pathogenesis of synucleinopathies due to its accumulation in typical protein aggregates in the brain. However, it is still unclear how it contributes to neurodegeneration. Type-2 diabetes mellitus is a risk factor for Parkinson's disease (PD). Interestingly, a common molecular alteration among these disorders is the age-associated increase in protein glycation. ...
Exacerbation of C1q dysregulation, synaptic loss and memory deficits in tau pat...
Carvalho, Kevin; Faivre, Emilie; Pietrowski, Marie J.; Marques, Xavier; Gomez-Murcia, Victoria; Deleau, Aude; Huin, Vincent; Hansen, Jan NAccumulating data support the role of tau pathology in cognitive decline in ageing and Alzheimer's disease, but underlying mechanisms remain ill-defined. Interestingly, ageing and Alzheimer's disease have been associated with an abnormal upregulation of adenosine A2A receptor (A2AR), a fine tuner of synaptic plasticity. However, the link between A2AR signalling and tau pathology has remained largely unexplored....
Novel players in the aging synapse: impact on cognition
Temido Ferreira, Mariana; Coelho, Joana E; Pousinha, Paula; Lopes, Luisa V.While neuronal loss has long been considered as the main contributor to age-related cognitive decline, these alterations are currently attributed to gradual synaptic dysfunction driven by calcium dyshomeostasis and alterations in ionotropic/metabotropic receptors. Given the key role of the hippocampus in encoding, storage, and retrieval of memory, the morpho- and electrophysiological alterations that occur in t...
Age-related shift in LTD is dependent on neuronal adenosine A2A receptors inter...
Temido Ferreira, Mariana; Ferreira, Diana; Batalha, Vânia; Marques-Morgado, Inês; Coelho, Joana E; Pereira, Pedro; Gomes, Rui; Pinto, AndreiaSynaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A2AR in age-related conditions. We report, for the first time, a significant overexpression o...
α-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 a...
Ferreira, Diana; Temido Ferreira, Mariana; Vicente Miranda, Hugo; Batalha, Vânia; Coelho, Joana E; Szegö, Éva M; Marques-Morgado, Inês; Vaz, Sandra H.Synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, are neurodegenerative disorders that are characterized by the accumulation of α-synuclein (aSyn) in intracellular inclusions known as Lewy bodies. Prefibrillar soluble aSyn oligomers, rather than larger inclusions, are currently considered to be crucial species underlying synaptic dysfunction. We identified the cellular prion protein ...
The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfuncti...
Batalha, Vânia; Ferreira, Diana; Coelho, Joana E; Valadas, Jorge S.; Gomes, Rui; Temido Ferreira, Mariana; Shmidt, Tatiana; Baqi, Younis; Buée, LucCaffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the human forebrain of aged and Alzheimer's disease (AD) patients. We have previously shown that an anti-A2AR therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian lev...