Mini review – The role of Glucocerebrosidase and Progranulin as possible targets in the treatment of Parkinson's disease

Rodrigues, P. S.; Kale, Pravin Popatrao

doi:10.1016/j.neurol.2021.01.015

Cited by 4 publications

(4 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In turn, sphingosine, as a result of phosphorylation, is converted into S1P, which has neuroprotective properties [ 50 ]. Our data confirm the advisability of using inhibitors of enzymes involved in the metabolism of glucosylceramides for the treatment of PD [ 51 , 52 ].…”

Section: Discussionsupporting

confidence: 83%

The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

et al. 2022

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

show abstract

Section: Discussionsupporting

confidence: 83%

The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

et al. 2022

View full text Add to dashboard Cite

show abstract

“…It has been previously reported that the concentration of progranulin was negatively correlated with an increase in the Hoehn-Yahr scale [67,71]. However, we did not detect any statistically significant differences in progranulin concentrations between the PD groups without and with dyskinesia [67][68][69][70]. Extracellularly, progranulin acts through the ephrin type-A receptor 2 (EphA2), exerting activities as an axonal growth factor and a neuronal survival factor.…”

Section: Discussioncontrasting

confidence: 68%

“…Progranulin is considered as a factor supporting the survival of neurons, among other things, by modulating neuroinflammation and by influencing neuronal lysosomes and autophagosomes [67,68]. Mutations in the gene coding for progranulin may lead to frontotemporal dementia, while the deficiency of progranulin itself may contribute to an increase in the concentration of α-synuclein, which may be directly associated with PD [69]. Paradoxically, progranulin may be secreted by activated microglia.…”

Section: Discussionmentioning

confidence: 99%

Adipokines, Vitamin D, and Selected Inflammatory Biomarkers among Parkinson’s Disease Patients with and without Dyskinesia: A Preliminary Examination

Milanowski,

Nuszkiewicz,

Lisewska

et al. 2024

Metabolites

View full text Add to dashboard Cite

Parkinson’s disease (PD), a widely recognized neurodegenerative disorder, is characterized by a spectrum of symptoms including motor fluctuations and dyskinesia. Neuroinflammation and dysregulation of adipokines are increasingly implicated in the progression of PD. This preliminary study investigated the levels of inflammatory biomarkers and adipokines, namely interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), visfatin, progranulin, and 25(OH)-vitamin D in 52 PD patients, divided equally between those with and without dyskinesia and 26 healthy controls. Significant differences in the levels of IL-6, TNF-α, visfatin, and progranulin were noted between the groups. Patients with dyskinesia exhibited notably higher IL-6 levels compared to controls, and TNF-α was significantly elevated in both PD patient groups relative to the control group. Additionally, visfatin levels were higher in PD patients without dyskinesia as opposed to those with dyskinesia, and progranulin levels were elevated in the non-dyskinetic PD group compared to controls. The findings highlight the potential role of the examined biomarkers in the pathophysiology of PD. Changes in levels of the tested inflammatory biomarkers and adipokines might be associated with Parkinson’s disease and its symptoms such as dyskinesia.

show abstract

“…GRN was also identified as one of the two main determinants of differential aging in the cerebral cortex 9 and as one of the five risk factors for limbic-predominant age-related TDP-43 encephalopathy (LATE) 10 . Polymorphisms in the GRN gene also contribute to the risk of Alzheimer's disease (AD) [11][12][13][14] and GRN is closely linked to Parkinson's disease (PD) 15,16 .…”

Section: Introductionmentioning

confidence: 99%

Progranulin inhibits phospholipase sPLA2-IIA to control neuroinflammation

Cha

Nana

et al. 2023

Preprint

View full text Add to dashboard Cite

Mutations in the granulin (GRN) gene, resulting in haploinsufficiency of the progranulin (PGRN) protein, are a leading cause of frontotemporal lobar degeneration (FTLD) and PGRN polymorphisms are associated with Alzheimer's disease (AD) and Parkinson's disease (PD). PGRN is a key regulator of microglia-mediated inflammation but the mechanism is still unknown. Here we report that PGRN interacts with sPLA2-IIA, a secreted phospholipase involved in inflammatory responses, to downregulate sPLA2-IIA activities and levels. sPLA2-IIA expression modifies PGRN deficiency phenotypes in mice and sPLA2-IIA inhibition rescues inflammation and lysosomal abnormalities in PGRN deficient mice. Furthermore, FTLD patients with GRN mutations show increased levels of sPLA2-IIA in astrocytes. Our data support sPLA2-IIA as a critical target for PGRN and a novel therapeutic target for FTLD-GRN.

show abstract

Mini review – The role of Glucocerebrosidase and Progranulin as possible targets in the treatment of Parkinson's disease

Cited by 4 publications

References 66 publications

The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

Adipokines, Vitamin D, and Selected Inflammatory Biomarkers among Parkinson’s Disease Patients with and without Dyskinesia: A Preliminary Examination

Progranulin inhibits phospholipase sPLA2-IIA to control neuroinflammation

Contact Info

Product

Resources

About