Investigational α-synuclein aggregation inhibitors: hope for Parkinson's disease.

Abstract

INTRODUCTION:

The therapeutic management of Parkinson's disease (PD) is challenging and has not been fully resolved. The main challenges include motor fluctuations and levodopa-induced dyskinesia. Moreover, no disease-modifying or neuroprotective therapy is currently available. Areas covered: This review focuses on α-synuclein aggregation inhibitors and their therapeutic role in PD, with special attention to heat shock proteins, immunotherapy (active and passive), the potential of targeting the Ser129 phosphorylation site, and the antibiotic possibilities. Expert opinion: The induction of chaperones may provide beneficial strategy to target synucleinopathies, but further investigations are needed to find the best options. The promising preclinical results with immunotherapy suggest that it may be a valuable disease-modifying therapy in PD in the future. Clinical trials are currently in the initial phases, and future studies need to confirm the beneficial therapeutic effect in humans and clarify open questions as regards the exact mode of action and potential safety concerns. In case of covalent modifications, phosphorylation of α-synuclein is of outstanding importance; however, conflicting results and open questions exist which necessitate clarification. In vitro results suggest that several antibiotics may also influence α-synuclein aggregation, but these results are to be confirmed in the future.

• Authors: Nóra Török, Zsófia Majláth, Levente Szalárdy, László Vécsei
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 25 Issue 11 Pg. 1281-1294 (Nov 2016) ISSN: 1744-7658 [Electronic] England
• PMID: 27677932 (Publication Type: Journal Article, Review)

Chemical References

• Antiparkinson Agents
• Drugs, Investigational
• Molecular Chaperones
• alpha-Synuclein

Topics

• Animals
• Antiparkinson Agents (pharmacology, therapeutic use)
• Drug Design
• Drugs, Investigational (pharmacology, therapeutic use)
• Humans
• Immunotherapy (methods)
• Molecular Chaperones (metabolism)
• Parkinson Disease (drug therapy, physiopathology)
• alpha-Synuclein (metabolism)