Journal article
Elucidation of the Structure and Synthesis of Neuroprotective Low Molecular Mass Components of the Parawixia bistriata Spider Venom
ACS chemical neuroscience, v 11(11), pp 1573-1596
03 Jun 2020
PMID: 32343555
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The South American social spider Parawixia bistriata produces a venom containing complex organic compounds with intriguing biological activities. The crude venom leads to paralysis in termites and stimulates L-glutamate uptake and inhibits GABA uptake in rat brain synaptosomes. Glutamate is the major neurotransmitter at the insect neuromuscular junction and at the mammalian central nervous system, suggesting a modulation of the glutamatergic system by the venom. Parawixin1, 2, and 10 (Pwx1, 2 and 10) are HPLC fractions that demonstrate this bioactivity. Pwx1 stimulates L-glutamate uptake through the main transporter in the brain, EAAT2, and is neuroprotective in in vivo glaucoma models. Pxw2 inhibits GABA and glycine uptake in synaptosomes and inhibits seizures and neurodegeneration, and Pwx10 increases L-glutamate uptake in synaptosomes and is neuroprotective and anticonvulsant, shown in in vivo epilepsy models. Herein, we investigated the low molecular mass compounds in this venom and have found over 20 small compounds and 36 unique acylpolyamines with and without amino acid linkers. The active substances in fractions Pwx1 and Pwx2 require further investigation. We elucidated and confirmed the structure of the active acylpolyamine in Pwx10. Both fraction Pwx10 and the synthesized component enhance the activity of transporters EAAT1 and EAAT2, and, importantly, offer in vitro neuroprotection against excitotoxicity in primary cultures. These data suggest that compounds with this mechanism could be developed into therapies for disorders in which L-glutamate excitotoxicity is involved.
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Details
- Title
- Elucidation of the Structure and Synthesis of Neuroprotective Low Molecular Mass Components of the Parawixia bistriata Spider Venom
- Creators
- Yvonne M. Forster - University of ZurichJennifer Leigh Green - Drexel UniversityApeksha Khatiwada - Drexel UniversityJose Luiz Liberato - Universidade de São PauloPoli Adi Narayana Reddy - The Wistar InstituteJoseph M. Salvino - The Wistar InstituteStefan Bienz - University of ZurichLaurent Bigler - University of ZurichWagner Ferreira dos Santos - Universidade de São PauloAndreia Cristina Karklin Fontana - Drexel University
- Publication Details
- ACS chemical neuroscience, v 11(11), pp 1573-1596
- Publisher
- American Chemical Society; Washington, DC
- Number of pages
- 24
- Grant note
- 2014/214192; 2005/60254-0 / Sao Paulo State Research Foundation (FAPESP, Brazil); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) Coordination for the Improvement of Higher Education Personnel (CAPES); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) Brazilian National Council for Scientific and Technological Development (CNPq); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Accelerated Career Entry Bachelor of Science in Nursing (BSN); Pharmacology and Physiology
- Web of Science ID
- WOS:000538519600009
- Scopus ID
- 2-s2.0-85085904115
- Other Identifier
- 991019312467904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Medicinal
- Neurosciences