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Predictors of drooling severity in people with Parkinson’s disease

Nascimento, David; Meira, Bruna; Garcez, Luís; Abreu, Daisy; Outeiro, Tiago; Guimarães, Isabel; Ferreira, Joaquim J.

Background Drooling, defned as the unintentional loss of saliva from the anterior oral cavity, remains poorly understood in terms of the underlying clinical factors in people with Parkinson’s disease (PwP). This study aims to clarify these factors by analyzing predictors and secondarily the correlates with the severity of drooling in PwP. Methods We conducted a cross-sectional study involving 42 PwP with drooli...


Lead as an environmental toxicant in models of synucleinopathies

Shvachiy, Liana; Amaro-Leal, Ângela; Machado, Filipa; Rocha, Isabel; Geraldes, Vera; Outeiro, Tiago

Lead, a toxic heavy metal, is prevalent in various industrial applications, contributing to environmental contamination and significant health concerns. Lead affects various body systems, especially the brain, causing long-lasting cognitive and behavioral changes. While most studies have focused on continuous lead exposure, intermittent exposure, such as that caused by migration or relocations, has received les...


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...


Defining the riddle in order to solve it: there is more than one “Parkinson's d...

Outeiro, Tiago; Alcalay, Roy N.; Antonini, Angelo; Attems, Johannes; Bonifati, Vincenzo; Cardoso, Francisco; Chesselet, Marie‐Françoise; Hardy, John

Background: More than 200 years after James Parkinsondescribed a clinical syndrome based on his astute observations, Parkinson's disease (PD) has evolved into a complex entity, akin to the heterogeneity of other complex human syndromes of the central nervous system such as dementia, motor neuron disease, multiple sclerosis, and epilepsy. Clinicians, pathologists, and basic science researchers evolved arrange of...


From molecular to functional effects of different environmental lead exposure p...

Shvachiy, Liana; Amaro-Leal, Ângela; Outeiro, Tiago; Rocha, Isabel; Geraldes, Vera

Lead is a heavy metal whose widespread use has resulted in environmental contamination and significant health problems, particularly if the exposure occurs during developmental stages. It is a cumulative toxicant that affects multiple systems of the body, including the cardiovascular and nervous systems. Chronic lead exposure has been defined as a cause of behavioral changes, inflammation, hypertension, and aut...


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, Bárbara

Alpha-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. ...


Inflammatory bowel disease, alpha-synuclein aggregates and Parkinson’s disease:...

Grunho, Miguel; Godinho, Catarina; Patita, Marta; Mocanu, Irina; Vieira, Ana Isabel; De Matos, António; Carregosa, Ricardo; Marx, Frederico

The hallmark of Parkinson’s disease (PD) is the accumulation of alpha-synuclein (AS) aggregates. Prior to the central nervous system involvement, PD establishes itself in the gut as a result of the complex interplay between microbiota, the host’s immune/neural systems and increased intestinal permeability. Inflammatory Bowel Disease (IBD) patients present a higher number of AS aggregates in the intestinal wall ...


Gut status in Parkinson’s disease: the GutSPark protocol

Grunho, Miguel; Godinho, Catarina; Matos, António Alves de; Barroso, Helena; Carregosa, Ricardo; Marx, Frederico; Tomé, Morgane; Domingos, Josefa

The neuropathological hallmark of Parkinson’s disease (PD) is the accumulation of alpha–synuclein (AS) aggregates. The identification of AS aggregates in gut biopsy specimens from people with PD may provide an opportunity to identify PD at a very early stage, prior to symptom onset. Changes in gut microbiota and inflammatory conditions (such as periodontitis) may be linked with PD onset/evolution. This project ...


MPV17 mutations are associated with a quiescent energetic metabolic profile

Jacinto, Sandra; Guerreiro, Patrícia; de Oliveira, Rita Machado; Cunha-Oliveira, Teresa; Santos, Maria João; Grazina, Manuela; Rego, Ana Cristina

Mutations in the MPV17 gene are associated with hepatocerebral form of mitochondrial depletion syndrome. The mechanisms through which MPV17 mutations cause respiratory chain dysfunction and mtDNA depletion is still unclear. The MPV17 gene encodes an inner membrane mitochondrial protein that was recently described to function as a non-selective channel. Although its exact function is unknown, it is thought to be...


Tapentadol prevents motor impairments in a mouse model of dyskinesia

Vaz, Rita; Chapela Pires, Diana; Coelho, Joana E; Lopes, Luisa V.; Ferreira, Joaquim J; Afonso, Nuno D.; Sousa, Sara; Outeiro, Tiago

The motor features in Parkinson's disease (PD) are associated with the degeneration of dopaminergic cells in the substantia nigra in the brain. Thus, the gold-standard in PD therapeutics still consists of dopamine replacement with levodopa. However, as the disease progresses, this therapeutic option becomes less effective and can be accompanied by levodopa-induced complications. On the other hand, several other...


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