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Parkinson's Disease is Predominantly a Genetic Disease.
J Parkinsons Dis
April 2024
Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
The discovery of a pathogenic variant in the alpha-synuclein (SNCA) gene in the Contursi kindred in 1997 indisputably confirmed a genetic cause in a subset of Parkinson's disease (PD) patients. Currently, pathogenic variants in one of the seven established PD genes or the strongest known risk factor gene, GBA1, are identified in ∼15% of PD patients unselected for age at onset and family history. In this Debate article, we highlight multiple avenues of research that suggest an important - and in some cases even predominant - role for genetics in PD aetiology, including familial clustering, high rates of monogenic PD in selected populations, and complete penetrance with certain forms.
View Article and Find Full Text PDFOptimizing aspirin dose for colorectal cancer patients through deep phenotyping using novel biomarkers of drug action.
Front Pharmacol
February 2024
University Hospital LB, Aragon Health Research Institute (IISAragon), CIBERehd, University of Zaragoza, Zaragoza, Spain.
Low-dose aspirin's mechanism of action for preventing colorectal cancer (CRC) is still debated, and the optimal dose remains uncertain. We aimed to optimize the aspirin dose for cancer prevention in CRC patients through deep phenotyping using innovative biomarkers for aspirin's action. We conducted a Phase II, open-label clinical trial in 34 CRC patients of both sexes randomized to receive enteric-coated aspirin 100 mg/d, 100 mg/BID, or 300 mg/d for 3 ± 1 weeks.
View Article and Find Full Text PDFBiomarkers of Response to Low-Dose Aspirin in Familial Adenomatous Polyposis Patients.
Cancers (Basel)
April 2023
Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University, 66100 Chieti, Italy.
Background: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial.
Methods: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas.
Results: In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B generation ex vivo (serum TXB).
Insight into CAZymes of FL18: Characterization of a New Multifunctional GH9 Enzyme.
Int J Mol Sci
December 2022
Department of Biology, University of Naples Federico II, 80126 Naples, Italy.
In the bio-based era, cellulolytic and hemicellulolytic enzymes are biocatalysts used in many industrial processes, playing a key role in the conversion of recalcitrant lignocellulosic waste biomasses. In this context, many thermophilic microorganisms are considered as convenient sources of carbohydrate-active enzymes (CAZymes). In this work, a functional genomic annotation of FL18, a recently discovered thermo-acidophilic microorganism, showed a wide reservoir of putative CAZymes.
View Article and Find Full Text PDFFL18 as a Novel Source of Glycosyl Hydrolases: Characterization of a New Thermophilic β-Xylosidase Tolerant to Monosaccharides.
Int J Mol Sci
November 2022
Department of Biology, University of Naples Federico II, Via Cinthia, 80126 Naples, Italy.
A thermo-acidophilic bacterium, FL18, was isolated from a hot spring of Pisciarelli, near Naples, Italy; following genome analysis, a novel putative β-xylosidase, AmβXyl, belonging to the glycosyl hydrolase (GH) family 3 was identified. A synthetic gene was produced, cloned in pET-30a(+), and expressed in BL21 (DE3) RIL. The purified recombinant protein, which showed a dimeric structure, had optimal catalytic activity at 80 °C and pH 5.
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