α-Synuclein and tau, two targets for dementia

Silva, Matias; Caro, Valentina; Guzmán, Camila; Perry, George; Areche, Carlos; Cornejo, Alberto

doi:10.1016/b978-0-12-819483-6.00001-1

Cited by 9 publications

(12 citation statements)

References 144 publications

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“…Interestingly, a polyphenol (-)-epigallocatechin gallate redirects the amyloid pathway preventing the formation of structures rich in b-sheet conformation through hydrogen bonds 34 . Moreover, these non-toxic elements do not provoke cytotoxicity in PC12 cells 13 .…”

Section: Discussionmentioning

confidence: 99%

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Dammarane triterpenes targeting α-synuclein: biological activity and evaluation of binding sites by molecular docking

Cornejo

Caballero

Simirgiotis

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Parkinson's disease (PD) is a neurodegenerative disorder that affects adult people whose treatment is palliative. Thus, we decided to test three dammarane triterpenes 1 , 1a , 1b , and we determined that 1 and 1a inhibit β-aggregation through thioflavine T rather than 1b . Since compound 1 was most active, we determined the interaction between α-synuclein and 1 at 50 µM (Kd) through microscale thermophoresis. Also, we observed differences in height and diameter of aggregates, and α-synuclein remains unfolded in the presence of 1 . Also, aggregates treated with 1 do not provoke neurites' retraction in N2a cells previously induced by retinoic acid. Finally, we studied the potential sites of interaction between 1 with α-synuclein fibrils using molecular modelling. Docking experiments suggest that 1 preferably interact with the site 2 of α-synuclein through hydrogen bonds with residues Y39 and T44.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, these non-toxic elements do not provoke cytotoxicity in PC12 cells 13 . Moreover, baicalein, a natural flavonoid, can prevent fibrillisation and disassembly of existing fibrils through the interaction of o-quinone with lysine forming a Schiff base 34 . Interestingly, baicalein can protect dopaminergic neurons in mice 35,36 .…”

Section: Discussionmentioning

confidence: 99%

Dammarane triterpenes targeting α-synuclein: biological activity and evaluation of binding sites by molecular docking

Cornejo

Caballero

Simirgiotis

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Other innovative treatments that were initially identified in preclinical studies are currently being evaluated in a number of clinical trials. These include antibody‐based treatments (anti–α‐synuclein, antitau), iron chelators, and α‐synuclein and tau aggregation inhibitors 38 . These treatments could potentially influence the course of disease and improve patients' and caregivers' quality of life.…”

Section: Advances In Radiopharmaceuticalsmentioning

confidence: 99%

“…These include antibody‐based treatments (anti–α‐synuclein, antitau), iron chelators, and α‐synuclein and tau aggregation inhibitors. 38 These treatments could potentially influence the course of disease and improve patients' and caregivers' quality of life. It also highlights the importance of developing early PET brain neurodegeneration biomarkers that closely reflect the pathophysiology of these diseases, to rapidly identify patient profiles that would benefit from being included in these therapeutic trials.…”

Section: Advances In Radiopharmaceuticalsmentioning

confidence: 99%

Single Photon Emission Computed Tomography/Positron Emission Tomography Molecular Imaging for Parkinsonism: A Fast‐Developing Field

Verger

Grimaldi

Ribeiro

et al. 2021

Annals of Neurology

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The early differential diagnosis of Parkinson disease and atypical parkinsonism is a major challenge. The use of single photon emission computed tomography (SPECT)/positron emission tomography (PET) molecular imaging to investigate parkinsonism is a fast-developing field. Imaging biomarker research may potentially lead to more accurate disease detection, enabling earlier diagnosis and treatment. This review summarizes recent SPECT/PET advances in radiopharmaceuticals and imaging technologies/analyses that improve the diagnosis of neurodegenerative parkinsonism. We are currently witnessing a turning point in the field. Integrating molecular imaging as a diagnostic technique represents an opportunity to reassess the strategies for diagnosing neurodegenerative parkinsonism.

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“…To date, there is no treatment to slow or stop the progression of the disease. At a time when treatments with disease-modifying potential are being developed (for example anti-synuclein antibodies or iron chelators) ( 2 ), identification of early markers of neurodegeneration is essential and these are urgently lacking.…”

Section: Introductionmentioning

confidence: 99%

Increased Sodium Concentration in Substantia Nigra in Early Parkinson's Disease: A Preliminary Study With Ultra-High Field (7T) MRI

et al. 2021

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Pathophysiology of idiopathic Parkinson's disease (iPD) is complex and still misunderstood. At a time when treatments with disease-modifying potential are being developed, identification of early markers of neurodegeneration is essential. Intracerebral sodium accumulation could be one of them. Indeed, it may be in relation to the mitochondrial dysfunction that early exists in iPD. For the first time, we used brain sodium (23Na) MRI to explore sodium concentration changes that have already been reported to be related to neurodegeneration in other diseases. We prospectively included 10 iPD patients (mean age 52.2 ± 5.9 years-old) with motor symptoms that started <36 months before inclusion and 12 healthy subjects (mean age 53 ± 6.4 years-old). Patients were scanned in OFF medication state by using proton (1H) and 23Na MRI at 7T. We then extracted quantitative Total Sodium Concentration (TSC) from five regions of interest known to be early impaired in iPD [substantia nigra (SN), putamen, caudate nucleus, pallidum, thalamus] and in one region supposed to be relatively spared in the first stages of the disease [cortical gray matter (neocortex)]. Potential atrophy in these structures was also investigated with 1H MRI. Relative to healthy subjects, iPD patients showed higher TSC in the SN (43.73 ± 4.64 vs. 37.72 ± 5.62, p = 0.006 after Bonferroni correction). A trend of increase in sodium concentrations was found within the pallidum (45.80 ± 4.19 vs. 41.07 ± 4.94, p = 0.017), putamen (48.65 ± 4.58 vs. 43.66 ± 5.04, p = 0.041) and the cortical gray matter (56.34 ± 3.92 vs. 50.81 ± 5.50, p = 0.021). No significant brain atrophy was found in patients compared to controls. Thus, alteration of sodium homeostasis in the SN in the absence of atrophy could be considered as a potential early marker of cellular dysfunction in iPD.

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α-Synuclein and tau, two targets for dementia

Cited by 9 publications

References 144 publications

Dammarane triterpenes targeting α-synuclein: biological activity and evaluation of binding sites by molecular docking

Dammarane triterpenes targeting α-synuclein: biological activity and evaluation of binding sites by molecular docking

Single Photon Emission Computed Tomography/Positron Emission Tomography Molecular Imaging for Parkinsonism: A Fast‐Developing Field

Increased Sodium Concentration in Substantia Nigra in Early Parkinson's Disease: A Preliminary Study With Ultra-High Field (7T) MRI

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