title: Neuroprotective and nootropic drug noopept rescues α-synuclein amyloid cytotoxicity.
abstract: Parkinson's disease is a common neurodegenerative disorder characterized by α-synuclein (α-Syn)-containing Lewy body formation and selective loss of dopaminergic neurons in the substantia nigra. We have demonstrated the modulating effect of noopept, a novel proline-containing dipeptide drug with nootropic and neuroprotective properties, on α-Syn oligomerization and fibrillation by using thioflavin T fluorescence, far-UV CD, and atomic force microscopy techniques. Noopept does not bind to a sterically specific site in the α-Syn molecule as revealed by heteronuclear two-dimensional NMR analysis, but due to hydrophobic interactions with toxic amyloid oligomers, it prompts their rapid sequestration into larger fibrillar amyloid aggregates. Consequently, this process rescues the cytotoxic effect of amyloid oligomers on neuroblastoma SH-SY5Y cells as demonstrated by using cell viability assays and fluorescent staining of apoptotic and necrotic cells and by assessing the level of intracellular oxidative stress. The mitigating effect of noopept against amyloid oligomeric cytotoxicity may offer additional benefits to the already well-established therapeutic functions of this new pharmaceutical.
authors: Department of Medical Biochemistry and Biophysics, Umeå University, SE-90187 Umeå, Sweden.
authors: Xueen
authors: X
authors: Jia
authors: Anna L
authors: AL
authors: Gharibyan
authors: Anders
authors: A
authors: Öhman
authors: Yonggang
authors: Y
authors: Liu
authors: Anders
authors: A
authors: Olofsson
authors: Ludmilla A
authors: LA
authors: Morozova-Roche
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D004151:Dipeptides / Q000494:pharmacology*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D058105:Polymerization / Q000187:drug effects*; D051844:alpha-Synuclein / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000682:Amyloid; D004151:Dipeptides; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D051844:alpha-Synuclein; C103871:ethyl phenylacetyl-Pro-Gly