scholarly journals Competing Endogenous RNA Networks as Biomarkers in Neurodegenerative Diseases

2020 ◽  
Vol 21 (24) ◽  
pp. 9582
Author(s):  
Leticia Moreno-García ◽  
Tresa López-Royo ◽  
Ana Cristina Calvo ◽  
Janne Markus Toivonen ◽  
Miriam de la Torre ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Spinocerebellar Ataxia Type ◽  
Competing Endogenous Rna ◽  
Regulate Gene Expression ◽  
Complex Disorders ◽  
Non Invasive ◽  
Complex Interactions ◽  
Spinocerebellar Ataxia Type 7 ◽  
Key Factor ◽  
The Central Nervous System

Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs. In this review, we summarize the ceRNA networks described in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and spinocerebellar ataxia type 7, and discuss their potential as biomarkers of these NDDs. Although numerous studies have been carried out, further research is needed to validate these complex interactions between RNAs and the alterations in RNA editing that could provide specific ceRNET profiles for neurodegenerative disorders, paving the way to a better understanding of these diseases.

scholarly journals Molecular and electrophysiological features of spinocerebellar ataxia type seven in induced pluripotent stem cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247434
Author(s):  
Richard J. Burman ◽  
Lauren M. Watson ◽  
Danielle C. Smith ◽  
Joseph V. Raimondo ◽  
Robea Ballo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Induced Pluripotent Stem Cells ◽  
Spinocerebellar Ataxia ◽  
Pluripotent Stem Cells ◽  
Spinocerebellar Ataxia Type ◽  
Patient Specific ◽  
Retinal Photoreceptors ◽  
Spinocerebellar Ataxia Type 7 ◽  
Induced Pluripotent

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the ATXN7 gene. Patients with this disease suffer from a degeneration of their cerebellar Purkinje neurons and retinal photoreceptors that result in a progressive ataxia and loss of vision. As with many neurodegenerative diseases, studies of pathogenesis have been hindered by a lack of disease-relevant models. To this end, we have generated induced pluripotent stem cells (iPSCs) from a cohort of SCA7 patients in South Africa. First, we differentiated the SCA7 affected iPSCs into neurons which showed evidence of a transcriptional phenotype affecting components of STAGA (ATXN7 and KAT2A) and the heat shock protein pathway (DNAJA1 and HSP70). We then performed electrophysiology on the SCA7 iPSC-derived neurons and found that these cells show features of functional aberrations. Lastly, we were able to differentiate the SCA7 iPSCs into retinal photoreceptors that also showed similar transcriptional aberrations to the SCA7 neurons. Our findings give technical insights on how iPSC-derived neurons and photoreceptors can be derived from SCA7 patients and demonstrate that these cells express molecular and electrophysiological differences that may be indicative of impaired neuronal health. We hope that these findings will contribute towards the ongoing efforts to establish the cell-derived models of neurodegenerative diseases that are needed to develop patient-specific treatments.

Current Limitations in the Treatment of Parkinson’s and Alzheimer’s Diseases: State-of-the-Art and Future Perspective of Polymeric Carriers

2019 ◽  
Vol 25 (41) ◽  
pp. 5755-5771 ◽  
Author(s):  
Chiara Tonda-Turo ◽  
Nicola Origlia ◽  
Clara Mattu ◽  
Alice Accorroni ◽  
Valeria Chiono
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Local Drug Delivery ◽  
Future Perspective ◽  
Non Invasive ◽  
Therapeutic Drugs ◽  
Parkinson’S Diseases ◽  
Polymeric Carriers ◽  
The Central Nervous System ◽  
The Moment

Alzheimer’s and Parkinson’s diseases are the most common neurodegenerative diseases worldwide and their incidence is increasing due to the aging population. At the moment, the available therapies are not disease modifying and have several limitations, some of which are discussed in this review. One of the main limitations of these treatments is the low concentration that drugs reach in the central nervous system after systemic administration. Indeed, the presence of biological barriers, particularly the blood-brain barrier (BBB), hinders the effective drug delivery to the brain, reducing the potential benefit coming from the administration of the medication. In this review, the mechanisms of transport across the BBB and new methods to improve drug passage across the BBB are discussed. These methods include non-invasive solutions such as intranasal and intravitreal administration, and the use of nanotechnology solutions based on polymeric carriers when the drug is intravenously injected, orally taken for intestine adsorption or delivered through the dermal mucosa. Also, it provides an analysis of more invasive solutions that include intracranially injected hydrogels and implanted devices for local drug delivery. Efforts in finding new therapeutic drugs blocking neurodegenerative disease progression or reverting their course should be coupled with efforts addressed to efficient drug delivery systems. Hence, new pharmacology discoveries together with advancements in nanotechnologies and biomaterials for regenerative medicine are required to effectively counteract neurodegenerative diseases.

scholarly journals Non-coding RNAs and the deregulation of ubiquitin-proteasome network in neurodegeneration: a familia tria?

2015 ◽  
Author(s):  
Stephan S Persengiev
Keyword(s):  
Neurodegenerative Diseases ◽  
Small Rna ◽  
Regulate Gene Expression ◽  
Brain Functions ◽  
Ubiquitin Proteasome ◽  
Development And Differentiation ◽  
The Central Nervous System ◽  
Gene Regulatory ◽  
Non Coding Rnas ◽  
Small Rna Species

Small non-coding RNAs (ncRNAs) represent a diverse group of gene regulatory factors that can posttranscriptionally regulate gene expression in response to various stimuli during brain development and differentiation. Subsets of ncRNAs and miRNAs in particular, are very specifically expressed within the central nervous system and participate in the regulation of important brain functions. miRNAs are essential for the postmitotic survival of neurons, and therefore might play a role in neuroprotection. A number of miRNAs have been reported to be dysregulated in several neurodegenerative diseases implying that they can contribute to pathogenesis. Furthermore, in light of the neuroprotective properties of some miRNAs, these small RNA species may themselves be the focus for drug development. Here, we review recent studies that imply a link between miRNA role in the regulation of ubiquitine-proteasome pathways and neurodegeneration and discuss how increased knowledge of miRNAs might serve the diagnosis and treatment of neurodegenerative diseases.

scholarly journals Salivary Redox Biomarkers in Selected Neurodegenerative Diseases

2020 ◽  
Vol 9 (2) ◽  
pp. 497 ◽  
Author(s):  
Mateusz Maciejczyk ◽  
Anna Zalewska ◽  
Karolina Gerreth
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Neuronal Apoptosis ◽  
Medical Personnel ◽  
Brain Inflammation ◽  
Non Invasive ◽  
Diagnosis And Prognosis ◽  
The Central Nervous System ◽  
Saliva Collection ◽  
Cerebral Degeneration

Neurodegenerative diseases (NDDs), such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are disorders, which cause irreversible and progressive deterioration of the central nervous system. The pathophysiology of NDDs is still not fully explained; nevertheless, oxidative stress is considered as a critical mediator of cerebral degeneration, brain inflammation, as well as neuronal apoptosis. Therefore, it is not surprising that redox biomarkers are increasingly used in the diagnosis of neurodegenerative diseases. As saliva is a very easy to obtain bioliquid, it seems promising to use this biomaterial in the diagnosis of NDDs. Saliva collection is easy, cheap, stress-free, and non-infectious, and it does not require the help of a specialised medical personnel. Additionally, the concentrations of many salivary redox biomarkers correlate with their content in blood serum as well as the degree of disease progression, which makes them non-invasive indicators of NDDs. This paper reviews the latest knowledge concerning the use of salivary redox biomarkers in the diagnosis and prognosis of selected neurodegenerative diseases.

scholarly journals Molecular and electrophysiological features of spinocerebellar ataxia type seven in induced pluripotent stem cells

2018 ◽  
Author(s):  
RJ Burman ◽  
LM Watson ◽  
DC Smith ◽  
JV Raimondo ◽  
R Ballo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Induced Pluripotent Stem Cells ◽  
Spinocerebellar Ataxia ◽  
Pluripotent Stem Cells ◽  
Spinocerebellar Ataxia Type ◽  
Patient Specific ◽  
Retinal Photoreceptors ◽  
Spinocerebellar Ataxia Type 7 ◽  
Induced Pluripotent

AbstractSpinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the ATXN7 gene. Patients with this disease suffer from a degeneration of their cerebellar Purkinje neurons and retinal photoreceptors that result in a progressive ataxia and loss of vision. As with many neurodegenerative diseases, studies of pathogenesis have been hindered by a lack of disease-relevant models. To this end, we have generated induced pluripotent stem cells (iPSCs) from a cohort of SCA7 patients in South Africa. First, we differentiated the SCA7 affected iPSCs into neurons which showed evidence of a transcriptional phenotype affecting components of STAGA (ATXN7 and KAT2A) and the heat shock protein pathway (DNAJA1 and HSP70). We then performed electrophysiology on the SCA7 iPSC-derived neurons and found that these cells show features of functional aberrations. Lastly, we were able to differentiate the SCA7 iPSCs into retinal photoreceptors that also showed similar transcriptional aberrations to the SCA7 neurons. Our findings demonstrate that iPSC-derived neurons and photoreceptors from SCA7 patients express molecular and electrophysiological differences that are indicative of impaired neuronal health. We hope that these findings will contribute towards the ongoing efforts to establish the cell-derived models of neurodegenerative diseases that are needed to develop patient-specific treatments.

Involvement of the Auditory Pathway in Spinocerebellar Ataxia Type 7

2021 ◽  
pp. 1-8
Author(s):  
Laura E. Ramos-Languren ◽  
Roberto Rodríguez-Labrada ◽  
Jonathan J. Magaña ◽  
Nalia Canales-Ochoa ◽  
Yanetza González-Zaldivar ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Auditory Evoked Potentials ◽  
Auditory Pathway ◽  
Cag Repeats ◽  
Spinocerebellar Ataxia Type ◽  
Autosomal Dominant Disorder ◽  
Significant Prolongation ◽  
Spinocerebellar Ataxia Type 7 ◽  
Functional Involvement ◽  
The Central Nervous System

<b><i>Background:</i></b> Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder caused by a mutation in the <i>ATXN7</i> gene. The involvement of the brainstem auditory pathway in pathogenesis of this disease has not been systematically assessed. <b><i>Aim:</i></b> To determine involvement of the brainstem auditory pathway in SCA7 patients and its relationship to clinical features of the disease. <b><i>Methods:</i></b> In this case-control study, brainstem auditory-evoked potentials (BAEPs) were assessed in 12 SCA7 patients with clinical and molecular diagnosis, compared to 2 control groups of 16 SCA2 patients and 16 healthy controls. <b><i>Results:</i></b> SCA7 patients exhibited significant prolongation of I-wave and III-wave latencies, whereas SCA2 patients showed increased latencies for III and V waves and I–III interpeak interval. SCA7 patients with larger I-wave latencies exhibited larger CAG repeats, earlier onset age, and higher SARA scores, but in SCA2 cases, these were not observed. <b><i>Conclusions:</i></b> BAEP tests revealed functional involvement of the auditory pathway in SCA7 (mainly at) peripheral portions, which gave new insights into the disease physiopathology different from SCA2 and may unravel distinct pathoanatomical effects of polyQ expansions in the central nervous system. <b><i>Significance:</i></b> These findings offer important insights into the distinctive disease mechanisms in SCA7 and SCA2, which could be useful for differential diagnosis and designing specific precision medicine approaches for both conditions.

scholarly journals Non-coding RNAs and the deregulation of ubiquitin-proteasome network in neurodegeneration: a familia tria?

2015 ◽  
Author(s):  
Stephan S Persengiev
Keyword(s):  
Neurodegenerative Diseases ◽  
Small Rna ◽  
Regulate Gene Expression ◽  
Brain Functions ◽  
Ubiquitin Proteasome ◽  
Development And Differentiation ◽  
The Central Nervous System ◽  
Gene Regulatory ◽  
Non Coding Rnas ◽  
Small Rna Species

Small non-coding RNAs (ncRNAs) represent a diverse group of gene regulatory factors that can posttranscriptionally regulate gene expression in response to various stimuli during brain development and differentiation. Subsets of ncRNAs and miRNAs in particular, are very specifically expressed within the central nervous system and participate in the regulation of important brain functions. miRNAs are essential for the postmitotic survival of neurons, and therefore might play a role in neuroprotection. A number of miRNAs have been reported to be dysregulated in several neurodegenerative diseases implying that they can contribute to pathogenesis. Furthermore, in light of the neuroprotective properties of some miRNAs, these small RNA species may themselves be the focus for drug development. Here, we review recent studies that imply a link between miRNA role in the regulation of ubiquitine-proteasome pathways and neurodegeneration and discuss how increased knowledge of miRNAs might serve the diagnosis and treatment of neurodegenerative diseases.

Natural Products for the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Rapid Development ◽  
New Drugs ◽  
Progressive Degeneration ◽  
Cord Injury ◽  
The Central Nervous System ◽  
And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer&#039;s Disease (AD), Parkinson&#039;s Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

scholarly journals Multiple Sclerosis Biomarker Discoveries by Proteomics and Metabolomics Approaches

2021 ◽  
Vol 16 ◽  
pp. 117727192110133
Author(s):  
Ameneh Jafari ◽  
Amirhesam Babajani ◽  
Mostafa Rezaei-Tavirani
Keyword(s):  
Multiple Sclerosis ◽  
Complex Disease ◽  
Biomarker Discovery ◽  
Response To Treatment ◽  
Inflammatory Disorder ◽  
Protein Marker ◽  
Complex Disorders ◽  
New Information ◽  
The Central Nervous System ◽  
Monitoring Treatment

Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system (CNS) resulting in demyelination and axonal loss in the brain and spinal cord. The precise pathogenesis and etiology of this complex disease are still a mystery. Despite many studies that have been aimed to identify biomarkers, no protein marker has yet been approved for MS. There is urgently needed for biomarkers, which could clarify pathology, monitor disease progression, response to treatment, and prognosis in MS. Proteomics and metabolomics analysis are powerful tools to identify putative and novel candidate biomarkers. Different human compartments analysis using proteomics, metabolomics, and bioinformatics approaches has generated new information for further clarification of MS pathology, elucidating the mechanisms of the disease, finding new targets, and monitoring treatment response. Overall, omics approaches can develop different therapeutic and diagnostic aspects of complex disorders such as multiple sclerosis, from biomarker discovery to personalized medicine.

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