scholarly journals Roles of Non-Coding RNAs as Novel Diagnostic Biomarkers in Parkinson’s Disease

2021 ◽  
pp. 1-15
Author(s):  
Ida Manna ◽  
Andrea Quattrone ◽  
Selene De Benedittis ◽  
Enrico Iaccino ◽  
Aldo Quattrone

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 5%of the elderly population. Currently, the diagnosis of PD is mainly based on clinical features and no definitive diagnostic biomarkers have been identified. The discovery of biomarkers at the earliest stages of PD is of extreme interest. This review focuses on the current findings in the field of circulating non-coding RNAs in PD. We briefly describe the more established circulating biomarkers in PD and provide a more thorough review of non-coding RNAs, in particular microRNAs, long non-coding RNAs and circular RNAs, differentially expressed in PD, highlighting their potential for being considered as biomarkers for diagnosis. Together, these studies hold promise for the use of peripheral biomarkers for the diagnosis of PD.

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Changjing Wang ◽  
Tongtong Yang ◽  
Meiyu Liang ◽  
Junxia Xie ◽  
Ning Song

AbstractParkinson’s disease (PD) is a common neurodegenerative disorder that primarily affects the elderly. While the etiology of PD is likely multifactorial with the involvement of genetic, environmental, aging and other factors, α-synuclein (α-syn) pathology is a pivotal mechanism underlying the development of PD. In recent years, astrocytes have attracted considerable attention in the field. Although astrocytes perform a variety of physiological functions in the brain, they are pivotal mediators of α-syn toxicity since they internalize α-syn released from damaged neurons, and this triggers an inflammatory response, protein degradation dysfunction, mitochondrial dysfunction and endoplasmic reticulum stress. Astrocytes are indispensable coordinators in the background of several genetic mutations, including PARK7, GBA1, LRRK2, ATP13A2, PINK1, PRKN and PLA2G6. As the most abundant glial cells in the brain, functional astrocytes can be replenished and even converted to functional neurons. In this review, we discuss astrocyte dysfunction in PD with an emphasis on α-syn toxicity and genetic modulation and conclude that astrocyte replenishment is a valuable therapeutic approach in PD.


2021 ◽  
Vol 14 ◽  
Author(s):  
Yimin Yang ◽  
Yanhua Li ◽  
Hongmei Yang ◽  
Jianxing Guo ◽  
Nan Li

Parkinson’s disease (PD) is the world’s second most common neurodegenerative disease that is associated with age. With the aging of the population, patients with PD are increasing in number year by year. Most such patients lose their ability to self-care with disease progression, which brings an incalculable burden to individual families and society. The pathogenesis of PD is complex, and its clinical manifestations are diverse. Therefore, it is of great significance to screen for circulating biomarkers associated with PD to reveal its pathogenesis and develop objective diagnostic methods so as to prevent, control, and treat the disease. In recent years, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are considered to be effective biomarkers for various diseases due to their stability, and resistance to RNAase digestion and extreme conditions in circulating fluids. Here, we review recent advances in the detection of abnormally expressed miRNAs and lncRNAs in PD circulating fluids, and discuss the function and molecular mechanisms of plasma or serum miR-124, miR-132, miR-29, miR-221, miR-7, miR-433, and miR-153 in the regulation and progression of PD. Additionally, application of the differential expression of lncRNAs in circulating fluid in the pathological progression and diagnosis of PD is also reviewed. In short, the determination of abnormally expressed circulating miRNAs and lncRNAs will be valuable for the future diagnosis and treatment of PD.


2021 ◽  
Vol 44 (1) ◽  
pp. 87-108
Author(s):  
Gabriel E. Vázquez-Vélez ◽  
Huda Y. Zoghbi

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by degeneration of the substantia nigra pars compacta and by accumulation of α-synuclein in Lewy bodies. PD is caused by a combination of environmental factors and genetic variants. These variants range from highly penetrant Mendelian alleles to alleles that only modestly increase disease risk. Here, we review what is known about the genetics of PD. We also describe how PD genetics have solidified the role of endosomal, lysosomal, and mitochondrial dysfunction in PD pathophysiology. Finally, we highlight how all three pathways are affected by α-synuclein and how this knowledge may be harnessed for the development of disease-modifying therapeutics.


2020 ◽  
Vol 21 (18) ◽  
pp. 6513 ◽  
Author(s):  
Shubhra Acharya ◽  
Antonio Salgado-Somoza ◽  
Francesca Maria Stefanizzi ◽  
Andrew I. Lumley ◽  
Lu Zhang ◽  
...  

Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data.


2020 ◽  
Vol 40 (19) ◽  
Author(s):  
Yasir H. Qureshi ◽  
Penelope Baez ◽  
Christiane Reitz

ABSTRACT Neuronal ceroid lipofuscinosis (NCL) is one of the most prevalent neurodegenerative disorders of early life, Parkinson’s disease (PD) is the most common neurodegenerative disorder of midlife, while Alzheimer’s disease (AD) is the most common neurodegenerative disorder of late life. While they are phenotypically distinct, recent studies suggest that they share a biological pathway, retromer-dependent endosomal trafficking. A retromer is a multimodular protein assembly critical for sorting and trafficking cargo out of the endosome. As a lysosomal storage disease, all 13 of NCL’s causative genes affect endolysosomal function, and at least four have been directly linked to retromer. PD has several known causative genes, with one directly linked to retromer and others causing endolysosomal dysfunction. AD has over 25 causative genes/risk factors, with several of them linked to retromer or endosomal trafficking dysfunction. In this article, we summarize the emerging evidence on the association of genes causing NCL with retromer function and endosomal trafficking, review the recent evidence linking NCL genes to AD, and discuss how NCL, AD, and PD converge on a shared molecular pathway. We also discuss this pathway’s role in microglia and neurons, cell populations which are critical to proper brain homeostasis and whose dysfunction plays a key role in neurodegeneration.


2020 ◽  
Vol 21 (12) ◽  
pp. 4250
Author(s):  
Yuzuru Imai

Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by age-dependent motor dysfunction and degeneration of the midbrain dopaminergic neurons [...]


2020 ◽  
Vol 20 (9) ◽  
pp. 754-767 ◽  
Author(s):  
Bianca L.B. Marino ◽  
Lucilene R. de Souza ◽  
Kessia P.A. Sousa ◽  
Jaderson V. Ferreira ◽  
Elias C. Padilha ◽  
...  

: Parkinson's Disease (PD) is the second most common neurodegenerative disease in the elderly population, with a higher prevalence in men, independent of race and social class; it affects approximately 1.5 to 2.0% of the elderly population over 60 years and 4% for those over 80 years of age. PD is caused by the necrosis of dopaminergic neurons in the substantia nigra, which is the brain region responsible for the synthesis of the neurotransmitter dopamine (DA), resulting in its decrease in the synaptic cleft. The monoamine oxidase B (MAO-B) degrades dopamine, promoting the glutamate accumulation and oxidative stress with the release of free radicals, causing excitotoxicity. The PD symptoms are progressive physical limitations such as rigidity, bradykinesia, tremor, postural instability and disability in functional performance. Considering that there are no laboratory tests, biomarkers or imaging studies to confirm the disease, the diagnosis of PD is made by analyzing the motor features. There is no cure for PD, and the pharmacological treatment consists of a dopaminergic supplement with levodopa, COMT inhibitors, anticholinergics agents, dopaminergic agonists, and inhibitors of MAO-B, which basically aims to control the symptoms, enabling better functional mobility and increasing life expectancy of the treated PD patients. Due to the importance and increasing prevalence of PD in the world, this study reviews information on the pathophysiology, symptomatology as well as the most current and relevant treatments of PD patients.


2001 ◽  
Vol 1 ◽  
pp. 207-208 ◽  
Author(s):  
Todd B. Sherer ◽  
Ranjita Betarbet ◽  
J. Timothy Greenamyre

Parkinson’s disease (PD), a common neurodegenerative disorder affects approximately 1% of the population over 65. PD is a late-onset progressive motor disease characterized by tremor, rigidity (stiffness), and bradykinesia (slowness of movement). The hallmark of PD is the selective death of dopamine-containing neurons in the substantia nigra pars compacta which send their projections to the striatum and the presence of cytoplasmic aggregates called Lewy bodies [1-2]. Most cases of PD are sporadic but rare cases are familial, with earlier onset. The underlying mechanisms and causes of PD still remain unclear.


2014 ◽  
Vol 262 (2) ◽  
pp. 451-458 ◽  
Author(s):  
Inga Liepelt-Scarfone ◽  
Stefanie Lerche ◽  
Stefanie Behnke ◽  
Jana Godau ◽  
Alexandra Gaenslen ◽  
...  

2009 ◽  
Vol 4 (1) ◽  
pp. 25 ◽  
Author(s):  
Angelo Antonini ◽  

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and is responsible for significant morbidity and costs. Non-motor manifestations of PD can be as disabling as the classic motor symptoms. Moreover, medications used to treat PD motor symptoms may have variable effects on these non-motor domains.


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