A5013150457- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Alzheimer's disease research and treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Nerve injury and regeneration
- Genetic Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- Curcumin's Biomedical Applications
- Botulinum Toxin and Related Neurological Disorders
- Skin and Cellular Biology Research
- RNA regulation and disease
- Cellular transport and secretion
- Galectins and Cancer Biology
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- 14-3-3 protein interactions
- Acupuncture Treatment Research Studies
- Pain Mechanisms and Treatments
- Barrier Structure and Function Studies
- Computational Drug Discovery Methods
- Estrogen and related hormone effects
- Metabolism, Diabetes, and Cancer
- Infective Endocarditis Diagnosis and Management
- Plasma and Flow Control in Aerodynamics
- Genomics, phytochemicals, and oxidative stress
- Diabetes Treatment and Management
Aarhus University
2016-2022
Danish Diabetes Academy
2021
Critical Software (Portugal)
2018
Universidade do Porto
2007-2016
Instituto de Biologia Molecular e Celular
2008-2015
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2015
The conversion of endogenous alpha-synuclein (asyn) to pathological asyn-enriched aggregates is a hallmark Parkinson's disease (PD). These inclusions can be detected in the central and enteric nervous system (ENS). Moreover, gastrointestinal symptoms appear up 20 years before diagnosis PD. dual-hit hypothesis posits that asyn aggregation starts ENS, retrogradely spreads brain. In this study, we tested by directly injecting preformed fibrils into duodenum wall wild-type rats transgenic with...
Abstract Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological aggregation. Native state stabilizers are promising drugs to treat Here we repurpose tolcapone, an FDA-approved molecule for Parkinson’s disease, as potent aggregation inhibitor. Tolcapone binds specifically human plasma, stabilizes the native vivo mice and humans inhibits cytotoxicity. Crystal structures of tolcapone bound wild-type V122I...
TTR binds to by electron microscopy (View interaction)
MINT‐7294529: TTR (uniprotkb:P02766) and bind (MI:0407) by comigration in non‐denaturing gel electrophoresis (MI:0404)
Abstract Neuronal aggregates of misfolded alpha-synuclein protein are found in the brain and periphery patients with Parkinson’s disease. Braak colleagues have hypothesized that initial formation may start gut, then spread to via peripheral autonomic nerves hereby affecting several organs, including heart intestine. Age is considered greatest risk factor for disease, but effect age on pathology its propagation has not been studied detail. We aimed investigate whether from gut more efficient...
Abstract Pathology consisting of intracellular aggregates alpha-Synuclein (α-Syn) spread through the nervous system in a variety neurodegenerative disorders including Parkinson’s disease, dementia with Lewy bodies, and multiple atrophy. The discovery structurally distinct α-Syn polymorphs, so-called strains, supports hypothesis where strain-specific structures are templated into formed by native α-Syn. These strains hypothesised to dictate spreading pathology tissue cellular impact...
Abstract Pain is a common non-motor symptom of Parkinson’s disease (PD), with current limited knowledge its pathophysiology. Here, we show that peripheral inoculation mouse alpha-synuclein (α-Syn) pre-formed fibrils, in transgenic model PD, elicited retrograde trans-synaptic spreading α-Syn pathology (pSer129) across sensory neurons and dorsal nerve roots, reaching central pain processing regions, including the spinal horn projections anterolateral system nervous (CNS). Pathological to CNS...
Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease caused by the extracellular deposition of mutant transthyretin (TTR), with special involvement peripheral nervous system (PNS). Currently, hepatic transplantation considered most efficient therapy to halt progression clinical symptoms in FAP since more than 95% TTR produced liver. However, less invasive and reliable therapeutic approaches have been proposed for therapy, namely based on drugs acting as inhibitors amyloid...
Abstract Here we describe the use of an organotypic hippocampal slice model for studying α-synuclein aggregation and inter-neuronal spreading initiated by microinjection pre-formed fibrils (PFFs). PFF injection at dentate gyrus (DG) templates formation endogenous aggregates in axons cell bodies this region that spread to CA3 CA1 regions. Aggregates are insoluble phosphorylated serine-129, recapitulating Lewy pathology features found Parkinson’s disease other synucleinopathies. The was favor...
Parkinson disease (PD) is the second most common neurodegenerative disorder and leading cause of motor disability. Pathologic accumulation aggregated alpha synuclein (AS) protein in brain, imbalance nigrostriatal system due to loss dopaminergic neurons substantia nigra- pars compacta, are hallmark features PD. AS aggregation propagation considered trigger neurotoxic mechanisms PD, including mitochondrial deficits oxidative stress. The eukaryotic elongation factor-2 kinase (eEF2K) mediates...
Transthyretin (TTR) amyloidoses comprise a wide spectrum of acquired and hereditary diseases triggered by extracellular deposition toxic TTR aggregates in various organs. Despite recent advances regarding the elucidation molecular mechanisms underlying misfolding pathogenic self-assembly, there is still no effective therapy for treatment these fatal disorders. Recently, "molecular tweezers", CLR01, has been reported to inhibit self-assembly toxicity different amyloidogenic proteins vitro,...
Abstract Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation toxic transthyretin aggregates fibrils, particularly in the peripheral nervous system. Since are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy treatment outcome. In this study, we evaluate protective effect physiologically achievable doses curcumin on...
Abstract Circumstantial evidence points to a pathological role of alpha-synuclein (aSyn; gene symbol SNCA ), conferred by aSyn misfolding and aggregation, in Parkinson disease (PD) related synucleinopathies. Several findings experimental models implicate perturbations the tissue homeostatic mechanisms triggered accumulation, including impaired redox homeostasis, as significant contributors pathogenesis PD. The nuclear factor erythroid 2-related (NRF2/Nrf2) is recognized ‘the master regulator...
Accumulation of aggregated alpha-synuclein (α-syn) is believed to play a pivotal role in the pathophysiology Parkinson's disease (PD) and other synucleinopathies. As key constituent Lewy pathology, more than 90% α-syn bodies phosphorylated at serine-129 (pS129) hence, it used extensively as marker for pathology. However, exact pS129 remains controversial kinase(s) responsible phosphorylation have yet be determined. In this study, we investigated effect Polo-like kinase 2 (PLK2) inhibition on...
Several natural polyphenols have been reported to act on different amyloidogenic proteins inhibiting amyloid formation therefore we decided test their effect transthyretin (TTR) formation. We found that epigallocatechin-3-gallate (EGCG), curcumin and nordihydroguaiaretic acid (NDGA) bind TTR modulate its amyloidogenicity, in vitro, although through mechanisms of action. Based these vitro studies, EGCG vivo using mice models for familial amyloidotic polyneuropathy (FAP). Therefore, performed...