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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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2022-10-01
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Series: | Frontiers in Pharmacology |
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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. |
first_indexed | 2024-04-11T19:13:11Z |
format | Article |
id | doaj.art-42aab74591674b57bb9f25c803e31101 |
institution | Directory Open Access Journal |
issn | 1663-9812 |
language | English |
last_indexed | 2024-04-11T19:13:11Z |
publishDate | 2022-10-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Pharmacology |
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 |
work_keys_str_mv | AT shivamkumarpandey recentdevelopmentsinnucleicacidbasedtherapiesforparkinsonsdiseasecurrentstatusclinicalpotentialandfuturestrategies AT rakeshkumarsingh recentdevelopmentsinnucleicacidbasedtherapiesforparkinsonsdiseasecurrentstatusclinicalpotentialandfuturestrategies |