Therapeutic innovation in Parkinson’s disease: a 2020 update on disease-modifying approaches

Colombo, Daniele; Pnevmatikou, Paraskevi; Melloni, Elsa; Keywood, Charlotte

doi:10.1080/14737175.2020.1800454

Cited by 14 publications

(6 citation statements)

References 165 publications

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“…PD is another common neurodegenerative disease associated with brain aging. The clinical appearances of PD are rigidity, bradykinesia, and rest tremor [87]. The pathology of PD includes the degeneration of dopaminergic neurons and the loss of dopamine in the substantia nigra and striatum [87,88].…”

Section: Circrnas In Pdmentioning

confidence: 99%

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Circular RNAs: emerging players in brain aging and neurodegenerative diseases

Zhao

Yan

et al. 2022

The Journal of Pathology

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Brain aging is closely related to neurodegenerative diseases. Circular RNAs (circRNAs) are a type of conserved RNAs with covalently closed continuous loops. Emerging evidence has shown that circRNAs are implicated in the biology of brain aging and the pathology of age-related neurodegenerative diseases. Here, we summarize current studies on circRNAs associated with brain aging and neurodegenerative diseases by discussing their expression features, pathophysiological roles, and mechanisms of action. We also discuss the potential challenges of circRNA-based therapy against brain aging and neurodegenerative diseases, as well as their potential as diagnostic biomarkers of neurodegenerative diseases. The review provides insights into current progress in the functions of circRNAs in the process of brain aging and neurodegenerative diseases.

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Section: Circrnas In Pdmentioning

confidence: 99%

“…The clinical appearances of PD are rigidity, bradykinesia, and rest tremor [87]. The pathology of PD includes the degeneration of dopaminergic neurons and the loss of dopamine in the substantia nigra and striatum [87,88]. Recent studies have indicated that circRNAs are associated with the pathological changes of PD.…”

Section: Circrnas In Pdmentioning

confidence: 99%

Circular RNAs: emerging players in brain aging and neurodegenerative diseases

Zhao

Yan

et al. 2022

The Journal of Pathology

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“…Several research groups are actively working to find an effective treatment for PD [ 147 ]. In this context, the SAA represents a valuable tool exploitable to monitor disease progression but overall to assess the effects of disease modifying treatments using easy to get biological tissues.…”

Section: Treatments For Pdmentioning

confidence: 99%

Approaching the Gut and Nasal Microbiota in Parkinson’s Disease in the Era of the Seed Amplification Assays

et al. 2022

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Parkinson’s disease (PD) is a neurodegenerative disorder often associated with pre-motor symptoms involving both gastrointestinal and olfactory tissues. PD patients frequently suffer from hyposmia, hyposalivation, dysphagia and gastrointestinal dysfunctions. During the last few years it has been speculated that microbial agents could play a crucial role in PD. In particular, alterations of the microbiota composition (dysbiosis) might contribute to the formation of misfolded α-synuclein, which is believed to be the leading cause of PD. However, while several findings confirmed that there might be an important link between intestinal microbiota alterations and PD onset, little is known about the potential contribution of the nasal microbiota. Here, we describe the latest findings on this topic by considering that more than 80% of patients with PD develop remarkable olfactory deficits in their prodromal disease stage. Therefore, the nasal microbiota might contribute to PD, eventually boosting the gut microbiota in promoting disease onset. Finally, we present the applications of the seed amplification assays to the study of the gut and olfactory mucosa of PD patients, and how they could be exploited to investigate whether pathogenic bacteria present in the gut and the nose might promote α-synuclein misfolding and aggregation.

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“…[1,4] In principle, these pieces of evidence suggest the potential of new therapeutic strategies aimed at lowering α-Syn production or increasing its clearance through the prevention and/or removal of its toxic aggregated deposits. [5] Many different approaches have been investigated in the last decade for preventing excessive buildup of α-Syn (a reduction by 25%-50% is expected to be sufficient to restore normal levels), and among them, the downregulation of SNCA gene expression attracted increasing interest in slowing or even stopping PD pathogenesis. [6] So far, promising results have been reached by epigenetic modification of SNCA through DNA methylation, [7] β2-adrenergic receptor agonists Clenbuterol and Salbutamol, [8] Gapmer-type antisense nucleotides, [9][10][11] short-interfering RNAs, [12] and small molecules acting on SNCA mRNAs.…”

Section: Introductionmentioning

confidence: 99%

Effective lowering of α-synuclein expression by targeting G-quadruplex structures within the SNCA gene

Pirota,

Rey,

Esposito

et al. 2024

Preprint

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Alpha-synuclein, encoded by the SNCA gene, is a pivotal protein implicated in the pathogenesis of synucleinopathies, including Parkinson's disease. Current approaches for modulating alpha-synuclein levels involve antisense nucleotides, siRNAs, and small molecules targeting SNCA's 5'-UTR mRNA. Here, we propose a groundbreaking strategy targeting G-quadruplex structures to effectively modulate SNCA gene expression and lowering alpha-synuclein amount. Novel G-quadruplex sequences, identified on the SNCA gene's transcription starting site and 5'-UTR of SNCA mRNAs, were experimentally confirmed for their stability through biophysical assays and in vitro experiments on human genomic DNA. Biological validation in differentiated SH-SY5Y cells revealed that well-known G-quadruplex ligands remarkably stabilized these structures, inducing the modulation of SNCA mRNAs expression, and the effective decrease in alpha-synuclein amount. Besides, a novel peptide nucleic acid conjugate, designed to selectively disrupt of G-quadruplex within the SNCA gene promoter, caused a promising lowering of both SNCA mRNA and alpha-synuclein protein. Altogether our findings highlight G-quadruplexes' key role as intriguing biological targets in achieving a notable and successful reduction in alpha-synuclein expression, pointing to a novel approach against synucleinopathies.

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Therapeutic innovation in Parkinson’s disease: a 2020 update on disease-modifying approaches

Cited by 14 publications

References 165 publications

Circular RNAs: emerging players in brain aging and neurodegenerative diseases

Circular RNAs: emerging players in brain aging and neurodegenerative diseases

Approaching the Gut and Nasal Microbiota in Parkinson’s Disease in the Era of the Seed Amplification Assays

Effective lowering of α-synuclein expression by targeting G-quadruplex structures within the SNCA gene

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