Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategies

Parkinson’s disease is the second most common progressive neurodegenerative disease diagnosed mainly based on clinical symptoms caused by loss of nigrostriatal dopaminergic neurons. Although currently available pharmacological therapies provide symptomatic relief, however, the disease continues to p...

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Main Authors: Shivam Kumar Pandey, Rakesh Kumar Singh
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.986668/full
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author Shivam Kumar Pandey
Rakesh Kumar Singh
author_facet Shivam Kumar Pandey
Rakesh Kumar Singh
author_sort Shivam Kumar Pandey
collection DOAJ
description Parkinson’s disease is the second most common progressive neurodegenerative disease diagnosed mainly based on clinical symptoms caused by loss of nigrostriatal dopaminergic neurons. Although currently available pharmacological therapies provide symptomatic relief, however, the disease continues to progress eventually leading to severe motor and cognitive decline and reduced quality of life. The hallmark pathology of Parkinson’s disease includes intraneuronal inclusions known as Lewy bodies and Lewy neurites, including fibrillar α-synuclein aggregates. These aggregates can progressively spread across synaptically connected brain regions leading to emergence of disease symptoms with time. The α-synuclein level is considered important in its fibrillization and aggregation. Nucleic acid therapeutics have recently been shown to be effective in treating various neurological diseases, raising the possibility of developing innovative molecular therapies for Parkinson’s disease. In this review, we have described the advancements in genetic dysregulations in Parkinson’s disease along with the disease-modifying strategies involved in genetic regulation with particular focus on downregulation of α-synuclein gene using various novel technologies, notably antisense oligonucleotides, microRNA, short interfering RNA, short hairpin RNAs, DNA aptamers, and gene therapy of vector-assisted delivery system-based therapeutics. In addition, the current status of preclinical and clinical development for nucleic acid-based therapies for Parkinson’s disease have also been discussed along with their limitations and opportunities.
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spelling doaj.art-42aab74591674b57bb9f25c803e311012022-12-22T04:07:30ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.986668986668Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategiesShivam Kumar PandeyRakesh Kumar SinghParkinson’s disease is the second most common progressive neurodegenerative disease diagnosed mainly based on clinical symptoms caused by loss of nigrostriatal dopaminergic neurons. Although currently available pharmacological therapies provide symptomatic relief, however, the disease continues to progress eventually leading to severe motor and cognitive decline and reduced quality of life. The hallmark pathology of Parkinson’s disease includes intraneuronal inclusions known as Lewy bodies and Lewy neurites, including fibrillar α-synuclein aggregates. These aggregates can progressively spread across synaptically connected brain regions leading to emergence of disease symptoms with time. The α-synuclein level is considered important in its fibrillization and aggregation. Nucleic acid therapeutics have recently been shown to be effective in treating various neurological diseases, raising the possibility of developing innovative molecular therapies for Parkinson’s disease. In this review, we have described the advancements in genetic dysregulations in Parkinson’s disease along with the disease-modifying strategies involved in genetic regulation with particular focus on downregulation of α-synuclein gene using various novel technologies, notably antisense oligonucleotides, microRNA, short interfering RNA, short hairpin RNAs, DNA aptamers, and gene therapy of vector-assisted delivery system-based therapeutics. In addition, the current status of preclinical and clinical development for nucleic acid-based therapies for Parkinson’s disease have also been discussed along with their limitations and opportunities.https://www.frontiersin.org/articles/10.3389/fphar.2022.986668/fullneurodegenerationα -synucleinmicroRNAshort interfering RNAshort hairpin RNAantisense oligonucleotides
spellingShingle Shivam Kumar Pandey
Rakesh Kumar Singh
Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategies
Frontiers in Pharmacology
neurodegeneration
α -synuclein
microRNA
short interfering RNA
short hairpin RNA
antisense oligonucleotides
title Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategies
title_full Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategies
title_fullStr Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategies
title_full_unstemmed Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategies
title_short Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategies
title_sort recent developments in nucleic acid based therapies for parkinson s disease current status clinical potential and future strategies
topic neurodegeneration
α -synuclein
microRNA
short interfering RNA
short hairpin RNA
antisense oligonucleotides
url https://www.frontiersin.org/articles/10.3389/fphar.2022.986668/full
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