14 documents found, page 1 of 2
Glycation of alpha-synuclein enhances aggregation and neuroinflammatory responses
Vasili, Eftychia; König, Annekatrin; Al-Azzani, Mohammed; Bosbach, Clara; Gatzemeier, Luisa Maria; Thom, Searlait; Chegão, Ana; Vicente Miranda, HugoPublisher Copyright: © The Author(s) 2025.; The risk of developing Parkinson’s disease (PD) is elevated in individuals with type 2 diabetes (T2DM), but the molecular pathways underlying this link remain unclear. Glycation, a non-enzymatic modification of lysine and arginine residues by reducing sugars or reactive dicarbonyls, may disrupt proteostasis and trigger pathology. Here, we investigated how methylglyoxa...
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...
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. ...
Insulin-degrading enzyme: an ally against metabolic and neurodegenerative diseases
Sousa, Luís; Guarda, Mariana; Meneses, Maria João; Macedo, M. Paula; Vicente Miranda, HugoInsulin-degrading enzyme (IDE) function goes far beyond its known proteolytic role as a regulator of insulin levels. IDE has a wide substrate promiscuity, degrading several proteins such as amyloid-β peptide, glucagon, islet amyloid polypeptide (IAPP), and insulin-like growth factors, which have diverse physiological and pathophysiological functions. Importantly, IDE plays other non-proteolytic functions such a...
Qual o verdadeiro impacto da intervenção coronária percutânea on‐site? Análise ...
Vicente Miranda, Hugo; Santos De Sousa, Catarina Isabel; Santos, Hélder; Almeida, Inês; Chin, Joana; Almeida, Samuel; Tavares, JoãoIntroduction: In an era in which coronary heart disease is one of the leading causes of death worldwide, several studies report the persistence of obstacles to accessing revascularization, and percutaneous coronary intervention in particular, which may be associated with worse outcomes. Objectives: To compare cardiovascular outcomes in patients admitted to hospitals with and without on-site percutaneous coronar...
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...
Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopat...
Vicente Miranda, Hugo; Szego, Éva M.; Oliveira, Luís M.A.; Breda, Carlo; Darendelioglu, Ekrem; de Oliveira, Rita M.; Ferreira, Diana G.α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with targe...
The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in...
de Oliveira, Rita Machado; Vicente Miranda, Hugo; Francelle, Laetitia; Pinho, Raquel; Szegö, Éva M.; Martinho, Renato; Munari, FrancescaSirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with age-associated neurodegenerative disorders such as Alzheimer and Parkinson disease (PD). However, the precise molecular mechanisms involved remain unclear. Here, we provide mechanistic insight into the interplay between sirtuin 2 and α-synucl...
Posttranslational modifications of blood-derived alpha-synuclein as biochemical...
Vicente Miranda, Hugo; Cassio, Rafaela; Correia Guedes, Leonor; Gomes, Marcos António; Chegão, Ana; Miranda, Elisa; Soares, Tiago; Coelho, MiguelParkinson's disease (PD) is a progressive neurodegenerative disorder known for the typical motor features associated. Pathologically, it is characterized by the intracellular accumulation of alpha-synuclein (aSyn) in Lewy bodies and Lewy neurites. Currently, there are no established biochemical markers for diagnosing or for following disease progression, a major limitation for the clinical practice. Posttransla...
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 ...