Abstract
The heterogeneity of symptoms and disease progression observed in synucleinopathies, of which Parkinsons disease (PD) is the most common representative, poses large problems for its treatment and for the discovery of novel therapeutics. The molecular basis for pathology is currently unclear, both in familial and in sporadic cases. While the therapeutic effects of L-DOPA and dopamine receptor agonists are still the gold standards for symptomatic treatment in PD, the development of neuroprotective and/or neurorestorative treatments for these disorders faces significant challenges due to the poor knowledge of the putative targets involved. Recent experimental evidence strongly suggests a central role for neurotoxic α-synuclein oligomeric species in neurodegeneration. The events leading to protein oligomerization, as well as the oligomeric species themselves, are likely amenable to modulation by small molecules, which are beginning to emerge in high throughput compound screens in a variety of model organisms. The therapeutic potential of small molecule modulators of oligomer formation demands further exploration and validation in cellular and animal disease models in order to accelerate human drug development.
Keywords: Parkinson's disease, drug discovery, quality control systems, aging, α-synuclein, synucleinopathies, aggregation, neurotoxic oligomers
Current Pharmaceutical Design
Title: Current and Future Therapeutic Strategies for Parkinsons Disease
Volume: 15 Issue: 34
Author(s): Tiago Fleming Outeiro and Joaquim Ferreira
Affiliation:
Keywords: Parkinson's disease, drug discovery, quality control systems, aging, α-synuclein, synucleinopathies, aggregation, neurotoxic oligomers
Abstract: The heterogeneity of symptoms and disease progression observed in synucleinopathies, of which Parkinsons disease (PD) is the most common representative, poses large problems for its treatment and for the discovery of novel therapeutics. The molecular basis for pathology is currently unclear, both in familial and in sporadic cases. While the therapeutic effects of L-DOPA and dopamine receptor agonists are still the gold standards for symptomatic treatment in PD, the development of neuroprotective and/or neurorestorative treatments for these disorders faces significant challenges due to the poor knowledge of the putative targets involved. Recent experimental evidence strongly suggests a central role for neurotoxic α-synuclein oligomeric species in neurodegeneration. The events leading to protein oligomerization, as well as the oligomeric species themselves, are likely amenable to modulation by small molecules, which are beginning to emerge in high throughput compound screens in a variety of model organisms. The therapeutic potential of small molecule modulators of oligomer formation demands further exploration and validation in cellular and animal disease models in order to accelerate human drug development.
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Cite this article as:
Outeiro Fleming Tiago and Ferreira Joaquim, Current and Future Therapeutic Strategies for Parkinsons Disease, Current Pharmaceutical Design 2009; 15 (34) . https://dx.doi.org/10.2174/138161209789649321
DOI https://dx.doi.org/10.2174/138161209789649321 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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