Marine-Derived Components: Can They Be a Potential Therapeutic Approach to Parkinson’s Disease?

Marine Drugs, Год журнала: 2023, Номер 21(8), С. 451 - 451

Опубликована: Авг. 16, 2023

The increase in the life expectancy average has led to a growing elderly population, thus leading prevalence of neurodegenerative disorders, such as Parkinson’s disease (PD). PD is second most common disorder and characterized by progressive degeneration dopaminergic neurons substantia nigra pars compacta (SNpc). marine environment proven be source unique diverse chemical structures with great therapeutic potential used treatment several pathologies, including impairments. This review focused on compounds isolated from organisms neuroprotective activities vitro vivo models based their structures, taxonomy, effects, possible mechanism action PD. About 60 bacteria, fungi, mollusk, sea cucumber, seaweed, soft coral, sponge, starfish therapy are reported. Peptides, alkaloids, quinones, terpenes, polysaccharides, polyphenols, lipids, pigments, mycotoxins were those organisms. They can act hallmarks, reducing oxidative stress, preventing mitochondrial dysfunction, α-synuclein aggregation, blocking inflammatory pathways through inhibition translocation NF-kB factor, reduction human tumor necrosis factor α (TNF-α), interleukin-6 (IL-6). gathers natural products that have shown pharmacological acting targets belonging different intracellular signaling related development, which should considered for future pre-clinical studies.

Язык: Английский

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Accurate long-read sequencing identified GBA1 as major risk factor in the Luxembourgish Parkinson’s study

npj Parkinson s Disease, Год журнала: 2023, Номер 9(1)

Опубликована: Ноя. 23, 2023

Abstract Heterozygous variants in the glucocerebrosidase GBA1 gene are an increasingly recognized risk factor for Parkinson’s disease (PD). Due to GBAP1 pseudogene, which shares 96% sequence homology with coding region, accurate variant calling by array-based or short-read sequencing methods remains a major challenge understanding genetic landscape of -associated PD. We analyzed 660 patients PD, 100 Parkinsonism and 808 healthy controls from Luxembourg study, sequenced using amplicon-based long-read DNA technology. found that 12.1% (77/637) PD carried variants, 10.5% (67/637) them carrying known pathogenic (including severe, mild, variants). In comparison, 5% (34/675) among them, 4.3% (29/675) were identified as carriers. four atypical parkinsonism. Pathogenic 2.6-fold more frequently observed compared (OR = 2.6; CI [1.6,4.1]). Three novel unknown significance (VUS) identified. Using structure-based approach, we defined potential prediction method VUS. This study describes full -related parkinsonism Luxembourg, showing high prevalence Although technique used our may be limited its effectiveness detect structural approach provides important advancement highly calling, is essential providing access emerging causative therapies

Язык: Английский

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Electric-field induced sleep promotion and lifespan extension in Gaucher's disease model flies

Biochemistry and Biophysics Reports, Год журнала: 2025, Номер 41, С. 101915 - 101915

Опубликована: Янв. 10, 2025

Язык: Английский

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Early-onset Parkinson's disease in a patient with a rare homozygous pathogenic GBA1 variant and no Gaucher disease symptoms

Neurogenetics, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 15, 2025

Язык: Английский

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Perspective Chapter: Next-Generation Sequencing and Variant Cataloging for Screening and Diagnosis of Sphingolipidoses and Mucopolysaccharidoses

IntechOpen eBooks, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

This chapter provides a comprehensive examination of how next-generation sequencing (NGS) technologies are transforming prenatal and neonatal care, particularly in the diagnosis lysosomal diseases (LDs). These rare, inherited conditions caused by defects metabolism. If not detected treated early, they can lead to significant disabilities reduced life expectancy. The specifically focuses on use NGS diagnose screen sphingolipidoses (SLDs) mucopolysaccharidoses (MPSs). It covers molecular pathogenesis, classification, main symptomatology diseases. reviews progress made identifying genes associated with SLDs MPSs cataloging clinically relevant genetic variants. Additionally, it highlights growing adoption for screening institutions such as academic research centers, private healthcare providers, government health agencies. also discusses challenges implementation, regulation, outlines future directions its application medicine.

Язык: Английский

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Activation and Purification of ß‐Glucocerebrosidase by Exploiting its Transporter LIMP‐2 – Implications for Novel Treatment Strategies in Gaucher's and Parkinson's Disease

Advanced Science, Год журнала: 2024, Номер 11(25)

Опубликована: Апрель 26, 2024

Abstract Genetic variants of GBA1 can cause the lysosomal storage disorder Gaucher disease and are among highest genetic risk factors for Parkinson's (PD). encodes enzyme beta‐glucocerebrosidase (GCase), which orchestrates degradation glucosylceramide (GluCer) in lysosome. Recent studies have shown that GluCer accelerates α ‐synuclein aggregation, exposing GCase deficiency as a major factor PD pathology promising target treatment. This study investigates interaction three disease‐associated (p.E326K, p.N370S, p.L444P) with their transporter, integral membrane protein 2 (LIMP‐2). Overexpression LIMP‐2 HEK 293T cells boosts abundance wt, E326K, N370S increases/rescues enzymatic activity wt E326K variant. Using novel purification approach, co‐purification untagged complex His‐tagged from cell supernatant 293F is achieved, confirming functional binding trafficking these variants. Furthermore, single helix ectodomain exploited to design lysosome‐targeted peptide enhances patient‐derived control fibroblasts. These findings reveal an allosteric activator GCase, suggesting possible therapeutic potential targeting this interaction.

Язык: Английский

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A Fixable Fluorescence‐Quenched Substrate for Quantitation of Lysosomal Glucocerebrosidase Activity in Both Live and Fixed Cells

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(40)

Опубликована: Авг. 16, 2023

Fluorogenic substrates are emerging tools that enable studying enzymatic processes within their native cellular environments. However, fluorogenic function live cells generally incompatible with fixation, preventing tandem application fundamental cell biology methods such as immunocytochemistry. Here we report a simple approach to the chemical fixation of dark-to-light substrate, LysoFix-GBA, which enables quantification glucocerebrosidase (GCase) activity in both and fixed cells. LysoFix-GBA measuring responses genetic perturbations lysosomal GCase activity. Further, permits multiplexed co-localization studies subcellular protein markers. This tool will aid role Parkinson's Disease, creating new therapeutic approaches targeting pathway. also lays foundation for an create fixable other enzymes.

Язык: Английский

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Soluble mannose receptor: A potential biomarker in Gaucher disease

European Journal Of Haematology, Год журнала: 2024, Номер 112(5), С. 794 - 801

Опубликована: Янв. 10, 2024

Abstract Purpose Soluble mannose receptor (sMR) relates to expression on macrophages, and is elevated in inflammatory disorders. Gaucher disease (GD) has altered macrophage function utilises receptors for enzyme replacement therapy (ERT) endocytosis. sMR not previously been studied GD. Methods was measured by ELISA correlated with GD clinical features including spleen liver volume, haemoglobin platelet count, bone marrow burden (BMB) scores immunoglobulin levels. compared biomarkers of GD: chitotriosidase, lyso‐GL1, PARC, CCL3, CCL4, osteoactivin, serum ACE ferritin. Results Median untreated patients 303.0 ng/mL post‐treatment 190.9 ( p = .02) healthy controls 202 ng/mL. median volume 455 mL r .70, .04), 2025 .64, BMB 7 .8, .03), IgA 1.9 g/L .54, .036), IgG 9.2 .57, .027), IgM 1.45 .86, < .0001), inverse correlation count 125 × 10 9 /L −.47, .08) 137 −.77, .0008). established biomarkers: osteoactivin 107.8 .58, .0006), chitotriosidase 3042 nmol/mL/h .52, PARC 800 .67, .0068), ferritin 547 μg/L .72, .002) CCL3 50 pg/mL .007). Conclusions correlates reduces following therapy.

Язык: Английский

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Iron Dyshomeostasis in Neurodegeneration with Brain Iron Accumulation (NBIA): Is It the Cause or the Effect?

Cells, Год журнала: 2024, Номер 13(16), С. 1376 - 1376

Опубликована: Авг. 19, 2024

Iron is an essential metal ion implicated in several cellular processes. However, the reactive nature of iron renders this potentially dangerous for cells, and its levels need to be tightly controlled. Alterations intracellular concentration are associated with different neuropathological conditions, including neurodegeneration brain accumulation (NBIA). As name suggests, NBIA encompasses a class rare still poorly investigated neurodegenerative disorders characterized by abnormal brain. mostly genetic pathology, date, 10 genes have been linked familial forms NBIA. In present review, after description principal mechanisms homeostasis, we summarize research data concerning pathological underlying discuss potential involvement such The picture that emerges that, while overload can contribute pathogenesis NBIA, it does not seem causal factor most pathology. onset these pathologies rather caused combination processes involving interplay between lipid metabolism, mitochondrial functions, autophagic activity, eventually leading dyshomeostasis.

Язык: Английский

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Comprehensive Analysis and Experimental Validation of the Parkinson’s Disease Lysosomal Gene ACP2 and Pan-cancer

Biochemical Genetics, Год журнала: 2024, Номер unknown

Опубликована: Фев. 3, 2024

Язык: Английский

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