Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era
The Authors. Medicinal Research Reviews published by Wiley Periodicals LLC..
Parkinson's disease (PD) is one of the most common neurodegenerative disorders that manifest various motor and nonmotor symptoms. Although currently available therapies can alleviate some of the symptoms, the disease continues to progress, leading eventually to severe motor and cognitive decline and reduced life expectancy. The past two decades have witnessed rapid progress in our understanding of the molecular and genetic pathogenesis of the disease, paving the way for the development of new therapeutic approaches to arrest or delay the neurodegenerative process. As a result of these advances, biomarker-driven subtyping is making it possible to stratify PD patients into more homogeneous subgroups that may better respond to potential genetic-molecular pathway targeted disease-modifying therapies. Therapeutic nucleic acid oligomers can bind to target gene sequences with very high specificity in a base-pairing manner and precisely modulate downstream molecular events. Recently, nucleic acid therapeutics have proven effective in the treatment of a number of severe neurological and neuromuscular disorders, drawing increasing attention to the possibility of developing novel molecular therapies for PD. In this review, we update the molecular pathogenesis of PD and discuss progress in the use of antisense oligonucleotides, small interfering RNAs, short hairpin RNAs, aptamers, and microRNA-based therapeutics to target critical elements in the pathogenesis of PD that could have the potential to modify disease progression. In addition, recent advances in the delivery of nucleic acid compounds across the blood-brain barrier and challenges facing PD clinical trials are also reviewed.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Medicinal research reviews - 40(2020), 6 vom: 18. Nov., Seite 2650-2681 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Dunhui [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.10.2021 Date Revised 28.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/med.21718 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM313424691 |
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| 245 | 1 | 0 | |a Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The Authors. Medicinal Research Reviews published by Wiley Periodicals LLC. | ||
| 520 | |a Parkinson's disease (PD) is one of the most common neurodegenerative disorders that manifest various motor and nonmotor symptoms. Although currently available therapies can alleviate some of the symptoms, the disease continues to progress, leading eventually to severe motor and cognitive decline and reduced life expectancy. The past two decades have witnessed rapid progress in our understanding of the molecular and genetic pathogenesis of the disease, paving the way for the development of new therapeutic approaches to arrest or delay the neurodegenerative process. As a result of these advances, biomarker-driven subtyping is making it possible to stratify PD patients into more homogeneous subgroups that may better respond to potential genetic-molecular pathway targeted disease-modifying therapies. Therapeutic nucleic acid oligomers can bind to target gene sequences with very high specificity in a base-pairing manner and precisely modulate downstream molecular events. Recently, nucleic acid therapeutics have proven effective in the treatment of a number of severe neurological and neuromuscular disorders, drawing increasing attention to the possibility of developing novel molecular therapies for PD. In this review, we update the molecular pathogenesis of PD and discuss progress in the use of antisense oligonucleotides, small interfering RNAs, short hairpin RNAs, aptamers, and microRNA-based therapeutics to target critical elements in the pathogenesis of PD that could have the potential to modify disease progression. In addition, recent advances in the delivery of nucleic acid compounds across the blood-brain barrier and challenges facing PD clinical trials are also reviewed | ||
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| 650 | 4 | |a Review | |
| 650 | 4 | |a Parkinson's disease | |
| 650 | 4 | |a blood-brain barrier | |
| 650 | 4 | |a molecular pathogenesis | |
| 650 | 4 | |a nucleic acid therapeutics | |
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| 700 | 1 | |a Fletcher, Sue |e verfasserin |4 aut | |
| 700 | 1 | |a Wilton, Steve D |e verfasserin |4 aut | |
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