New hopes for disease modification in Parkinson's Disease DOI Creative Commons
Werner Poewe, Klaus Seppi,

Kathrin Marini

et al.

Neuropharmacology, Journal Year: 2020, Volume and Issue: 171, P. 108085 - 108085

Published: April 13, 2020

To date, despite numerous clinical trials, no intervention has been demonstrated to modify the progression of Parkinson's disease (PD). However, over past decades encouraging progress made towards a better understanding molecular pathways relevant for neurodegenerative process in PD. This is also based on new insights into genetic architecture disease, revealing multiple novel targets potentially disease-modifying interventions. Important achievements have field risk markers and combinations thereof, form algorithms, will hopefully soon provide possibility identify affected individuals at yet prediagnostic or prodromal stages illness. Such phases would an ideal window neuroprotection trials. Taken together, these developments offer hope that breakthrough modifying course PD might be reached. In this article we summarize various approaches currently pursued quest. part special issue entitled 'The Quest Disease-Modifying Therapies Neurodegenerative Disorders'.

Language: Английский

Plasma Glucosylsphingosine in GBA1 Mutation Carriers with and without Parkinson's Disease DOI
Matthew Surface, Manisha Balwani, Cheryl Waters

et al.

Movement Disorders, Journal Year: 2021, Volume and Issue: 37(2), P. 416 - 421

Published: Nov. 6, 2021

ABSTRACT Background Biallelic mutations in the GBA1 gene encoding glucocerebrosidase cause Gaucher's disease, whereas heterozygous carriers are at risk for Parkinson's disease (PD). Glucosylsphingosine is a clinically meaningful biomarker of but could not be assayed previously carriers. Objective The aim this study was to assess plasma glucosylsphingosine levels N370S with and without PD. Methods Glucosylsphingosine, glucosylceramide, four other lipids were quantified from heterozygotes (n = 20) or PD, healthy controls 20), idiopathic PD homozygotes (positive controls; Gaucher's/PD) using quantitative ultra‐performance liquid chromatography tandem mass spectrometry. Results Plasma significantly higher compared noncarriers, independent status. As expected, Gaucher's/PD cases showed increases both substrates, glucosylceramide. Conclusions accumulation shown opens up its future assessment as ‐PD. © 2021 Authors. Movement Disorders published by Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Language: Английский

Citations

34
Interaction between autophagy and the NLRP3 inflammasome in Alzheimer’s and Parkinson’s disease DOI Creative Commons
Ranran Lu, Lijie Zhang, Xinling Yang

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Oct. 3, 2022

Autophagy degrades phagocytosed damaged organelles, misfolded proteins, and various pathogens through lysosomes as an essential way to maintain cellular homeostasis. is a tightly regulated self-degradation process that plays crucial role in maintaining normal function homeostasis the body. The NLRP3 inflammasome neuroinflammation vital recognition receptor innate immunity, sensing external invading endogenous stimuli further triggering inflammatory responses. forms complex by recognizing DAMPS or PAMPS, its activation triggers caspase-1-mediated cleavage of pro-IL-1β pro-IL-18 promote response. In recent years, it has been reported there interaction between autophagy neuroinflammation. Strengthening can regulate expression reduce neurodegenerative disease protect neurons. However, related mechanism not entirely clear. formation protein aggregates one standard features Neurodegenerative diseases. A large number toxic induce inflammation. theory, pathway remove potential toxicity delay progression disease. This article aims review research on autophagy, inflammasome, Alzheimer’s (AD) Parkinson’s (PD), analyze provide theoretical references for future.

Language: Английский

Citations

27
The Hidden Cell-to-Cell Trail of α-Synuclein Aggregates DOI Creative Commons
Sandesh Neupane, Elena De Cecco, Adriano Aguzzi

et al.

Journal of Molecular Biology, Journal Year: 2022, Volume and Issue: 435(12), P. 167930 - 167930

Published: Dec. 22, 2022

The progressive accumulation of insoluble aggregates the presynaptic protein alpha-synuclein (α-Syn) is a hallmark neurodegenerative disorders including Parkinson's disease (PD), Multiple System Atrophy, and Dementia with Lewy Bodies, commonly referred to as synucleinopathies. Despite considerable progress on structural biology these aggregates, molecular mechanisms mediating their cell-to-cell transmission, propagation, neurotoxicity remain only partially understood. Numerous studies have highlighted stereotypical spatiotemporal spreading pathological α-Syn across different tissues anatomically connected brain regions over time. Experimental evidence from various cellular animal models indicate that transfer occurs in two defined steps: release pathogenic species infected cells, uptake via passive or active endocytic pathways. Once been internalized, little known about what drives toxicity how they interact endogenous promote its misfolding subsequent aggregation. Similarly, unknown genetic factors modulate responses aggregation species. Here we discuss current understanding phenomena associated intercellular seeds summarize supporting transmission hypothesis. Understanding involved essential develop novel targeted therapeutics against PD related

Language: Английский

Citations

25
Lysosomal Ceramide Metabolism Disorders: Implications in Parkinson’s Disease DOI Open Access
Silvia Paciotti, Elisabetta Albi, Lucilla Parnetti

et al.

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(2), P. 594 - 594

Published: Feb. 21, 2020

Ceramides are a family of bioactive lipids belonging to the class sphingolipids. Sphingolipidoses group inherited genetic diseases characterized by unmetabolized sphingolipids and consequent reduction ceramide pool in lysosomes. include several disorders as Sandhoff disease, Fabry Gaucher metachromatic leukodystrophy, Krabbe Niemann Pick Farber GM2 gangliosidosis. In sphingolipidosis, lysosomal lipid storage occurs both central nervous system visceral tissues, pathology is common hallmark for all them. Parkinson's most neurodegenerative movement disorder, accumulation aggregation misfolded α-synuclein that seem associated some disorders, particular disease. This review provides evidence into role metabolism pathophysiology lysosomes, highlighting more recent findings on its involvement

Language: Английский

Citations

39
New hopes for disease modification in Parkinson's Disease DOI Creative Commons
Werner Poewe, Klaus Seppi,

Kathrin Marini

et al.

Neuropharmacology, Journal Year: 2020, Volume and Issue: 171, P. 108085 - 108085

Published: April 13, 2020

To date, despite numerous clinical trials, no intervention has been demonstrated to modify the progression of Parkinson's disease (PD). However, over past decades encouraging progress made towards a better understanding molecular pathways relevant for neurodegenerative process in PD. This is also based on new insights into genetic architecture disease, revealing multiple novel targets potentially disease-modifying interventions. Important achievements have field risk markers and combinations thereof, form algorithms, will hopefully soon provide possibility identify affected individuals at yet prediagnostic or prodromal stages illness. Such phases would an ideal window neuroprotection trials. Taken together, these developments offer hope that breakthrough modifying course PD might be reached. In this article we summarize various approaches currently pursued quest. part special issue entitled 'The Quest Disease-Modifying Therapies Neurodegenerative Disorders'.

Language: Английский

Citations

38