Expression characteristics of peripheral blood genes reveal potential biomarkers and candidate therapeutic targets for Parkinson's disease

Parkinson’s disease (PD) is a widespread neurodegenerative disorder. Despite the intensive studies of this pathology, in general, the picture of the etiopathogenesis has still not been clarified fully. To understand better the mechanisms underlying the pathogenesis of PD, we analyzed the expression of 10 genes in the peripheral blood of treated and untreated patients with PD. 35 untreated patients with PD and 12 treated patients with Parkinson’s disease (Hoehn and Yahr scores 1-2) were studied. An analysis of the mRNA levels ofATP13A2,PARK2,PARK7,PINK1,LRRK2,SNCA,ALDH1A1,PDHB,PPARGC1A, andZNF746genes in the peripheral blood of patients was carried out using reverse transcription followed by real-time PCR. A statistically significant and specific increase by more than 1.5-fold in the expression of theATP13A2,PARK7, andZNF746genes was observed in patients with PD. Based on these results, it can be suggested that the upregulation of the mRNA levels ofATP13A2,PARK7, andZNF746in untreated patients in the earliest clinical stages can also be observed in the preclinical stages of PD, and that these genes can be considered as potential biomarkers of the preclinical stage of PD.

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Content of Peripheral Blood T- and B-Cell Subpopulations in Transgenic A53T Mice of Different Age (A Model of Parkinson’s Disease)

Bulletin of Experimental Biology and Medicine ◽

10.1007/s10517-021-05075-w ◽

2021 ◽

Author(s):

G. V. Idova ◽

E. L. Al’perina ◽

M. M. Gevorgyan ◽

M. A. Tikhonova ◽

S. Ya. Zhanaeva

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

B Cell ◽

Peripheral Blood ◽

Cell Subpopulations

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Glucocerebrosidase Activity is Reduced in Cryopreserved Parkinson’s Disease Patient Monocytes and Inversely Correlates with Motor Severity

Journal of Parkinson s Disease ◽

10.3233/jpd-202508 ◽

2021 ◽

pp. 1-9

Author(s):

Laura P. Hughes ◽

Marilia M.M. Pereira ◽

Deborah A. Hammond ◽

John B. Kwok ◽

Glenda M. Halliday ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Rating Scale ◽

Disease Patient ◽

Motor Symptom ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Classical Monocytes

Background: Reduced activity of lysosomal glucocerebrosidase is found in brain tissue from Parkinson’s disease patients. Glucocerebrosidase is also highly expressed in peripheral blood monocytes where its activity is decreased in Parkinson’s disease patients, even in the absence of GBA mutation. Objective: To measure glucocerebrosidase activity in cryopreserved peripheral blood monocytes from 30 Parkinson’s disease patients and 30 matched controls and identify any clinical correlation with disease severity. Methods: Flow cytometry was used to measure lysosomal glucocerebrosidase activity in total, classical, intermediate, and non-classical monocytes. All participants underwent neurological examination and motor severity was assessed by the Movement Disorders Society Unified Parkinson’s Disease Rating Scale. Results: Glucocerebrosidase activity was significantly reduced in the total and classical monocyte populations from the Parkinson’s disease patients compared to controls. GCase activity in classical monocytes was inversely correlated to motor symptom severity. Conclusion: Significant differences in monocyte glucocerebrosidase activity can be detected in Parkinson’s disease patients using cryopreserved mononuclear cells and monocyte GCase activity correlated with motor features of disease. Being able to use cryopreserved cells will facilitate the larger multi-site trials needed to validate monocyte GCase activity as a Parkinson’s disease biomarker.

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Expression of MxA mRNA in peripheral blood mononuclear cells in Parkinson’s disease

Parkinsonism & Related Disorders ◽

10.1016/s1353-8020(98)00040-6 ◽

1999 ◽

Vol 5 (1-2) ◽

pp. 43-47 ◽

Cited By ~ 2

Author(s):

N. Kawaguchi ◽

T. Yamada ◽

M. Takahashi ◽

T. Hattori

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

International Journal of Molecular Sciences ◽

10.3390/ijms22073708 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3708

Author(s):

Jun Ogata ◽

Kentaro Hirao ◽

Kenya Nishioka ◽

Arisa Hayashida ◽

Yuanzhe Li ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Peripheral Blood ◽

Kinase Activity ◽

Late Onset ◽

Causative Gene ◽

Protein Levels ◽

Wd40 Domain ◽

Lrrk2 Protein ◽

Familial Parkinson’S Disease

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.

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