Abstract
Neurodegenerative disorders have been and remain persistent sources of enormous suffering throughout human history. The tragedy of their impact on human relationships, physical vitality, and fundamental dignity cannot be understated. Parkinson’s disease (PD), one of the most common of these terrible illnesses, has a global incidence of approximately two-to-four percent of the human population, along with devastating social and economic impact. The present review analyzes aspects of PD pathophysiology that offer particularly attractive strategies for the development of improved prevention and therapy. The occurrence, symptoms, pathogenesis, and etiology of PD are considered, with focus on how the Alpha synuclein protein, which normally regulates neurotransmitter release, is aggregated by oxidative stressors into toxic inclusions, prominently including Lewy bodies and insoluble fibrils that disrupt the organization of brain areas responsible for motor control. The contribution to a progressively prooxidant tissue environment resulting from interaction between advanced glycation end products (AGEs) and their cognate receptors (RAGEs) is examined here as a significant driver of PD. This review also explores strategies currently being developed by a U.S.-Russian team that may reduce the risk and severity of PD by use of recombinant atoxic derivatives (ad) of botulinum neurotoxins (BoNT/A ad), that traffic inducers of the cytoprotective enzyme heme oxygenase to selected midbrain neurons, at which Alpha synuclein aggregation occurs. Considered together, the topic material presented here provides both researchers and clinicians with a short but concise overview of the current understanding of PD pathology and approaches to biotherapeutic (precision) countermeasures to its onset and progression.
Keywords: Heme oxygenase, Parkinson’s disease, alpha synuclein, proteotoxic stress, aggregation, neurodegenerative disorders.
Current Pharmaceutical Design
Title:Parkinson’s Disease: Alpha Synuclein, Heme Oxygenase and Biotherapeutic Countermeasures
Volume: 24 Issue: 20
Author(s): David D. Haines*, Maxim V. Trushin, Stephen Rose, Iloki Assanga Simon Bernard and Fadia F. Mahmoud
Affiliation:
- Northwell Health System, New York, NY,United States
Keywords: Heme oxygenase, Parkinson’s disease, alpha synuclein, proteotoxic stress, aggregation, neurodegenerative disorders.
Abstract: Neurodegenerative disorders have been and remain persistent sources of enormous suffering throughout human history. The tragedy of their impact on human relationships, physical vitality, and fundamental dignity cannot be understated. Parkinson’s disease (PD), one of the most common of these terrible illnesses, has a global incidence of approximately two-to-four percent of the human population, along with devastating social and economic impact. The present review analyzes aspects of PD pathophysiology that offer particularly attractive strategies for the development of improved prevention and therapy. The occurrence, symptoms, pathogenesis, and etiology of PD are considered, with focus on how the Alpha synuclein protein, which normally regulates neurotransmitter release, is aggregated by oxidative stressors into toxic inclusions, prominently including Lewy bodies and insoluble fibrils that disrupt the organization of brain areas responsible for motor control. The contribution to a progressively prooxidant tissue environment resulting from interaction between advanced glycation end products (AGEs) and their cognate receptors (RAGEs) is examined here as a significant driver of PD. This review also explores strategies currently being developed by a U.S.-Russian team that may reduce the risk and severity of PD by use of recombinant atoxic derivatives (ad) of botulinum neurotoxins (BoNT/A ad), that traffic inducers of the cytoprotective enzyme heme oxygenase to selected midbrain neurons, at which Alpha synuclein aggregation occurs. Considered together, the topic material presented here provides both researchers and clinicians with a short but concise overview of the current understanding of PD pathology and approaches to biotherapeutic (precision) countermeasures to its onset and progression.
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Cite this article as:
Haines D. David *, Trushin V. Maxim , Rose Stephen , Bernard Assanga Simon Iloki and Mahmoud F. Fadia, Parkinson’s Disease: Alpha Synuclein, Heme Oxygenase and Biotherapeutic Countermeasures, Current Pharmaceutical Design 2018; 24 (20) . https://dx.doi.org/10.2174/1381612824666180717161338
DOI https://dx.doi.org/10.2174/1381612824666180717161338 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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