Aggregation and properties of α‒synuclein and related proteins

α-Synuclein has been identified as a component of intracellular fibrillar protein deposits in several neurodegenerative diseases, and two mutant forms have been associated with early onset Parkinson's disease. A fragment of α-synuclein has also been identified as the non-Aβ component of Alzheimer's disease amyloid (NAC). Ageing solutions of α-synuclein and NAC leads to formation of β-sheet, detectable by circular dichroism spectroscopy, and aggregation to form amyloid-like fibrils, detectable by electron microscopy. Differences in the rates of aggregation of the fibrils formed by α-synuclein and the two mutant proteins are presented. The toxicity of α-synuclein and related peptides towards neurons is also discussing in relation to the aetiology of neurodegenerative diseases.Experiments on fragments of NAC have enabled the region of NAC responsible for its aggregation and toxicity to be identified.

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Aggregation and neurotoxicity of α-synuclein and related peptides

Biochemical Society Transactions ◽

10.1042/bst0300559 ◽

2002 ◽

Vol 30 (4) ◽

pp. 559-565 ◽

Cited By ~ 97

Author(s):

O. M. A. EI-Agnaf ◽

G. B. Irvine

Keyword(s):

Electron Microscopy ◽

Antioxidant Properties ◽

Amyloid Β ◽

Cd Spectroscopy ◽

Amyloid Β Peptide ◽

Peptide Component ◽

Mutant Forms ◽

Β Sheet ◽

Early Onset Parkinson’S Disease ◽

Apoptotic Mechanism

Fibrillar deposits of α-synuclein occur in several neurodegenerative diseases. Two mutant forms of α-synuclein have been associated with early-onset Parkinson's disease, and a fragment has been identified as the non-amyloid-β peptide component of Alzheimer's disease amyloid (NAC). Upon aging, solutions of α-synuclein and NAC change conformation to β-sheet, detectable by CD spectroscopy, and form oligomers that deposit as amyloid-like fibrils, detectable by electron microscopy. These aged peptides are also neurotoxic. Experiments on fragments of NAC have enabled the region of NAC responsible for its aggregation and toxicity to be identified. NAC(8–18) is the smallest fragment that aggregates, as indicated by the concentration of peptide remaining in solution after 3 days, and forms fibrils, as determined by electron microscopy. Fragments NAC(8–18) and NAC(8–16) are toxic, whereas NAC(12–18), NAC(9–16) and NAC(8–15) are not. Hence residues 8–16 of NAC comprise the region crucial for toxicity. Toxicity induced by α-synuclein, NAC and NAC(1–18) oligomers occurs via an apoptotic mechanism, possibly initiated by oxidative damage, since these peptides liberate hydroxyl radicals in the presence of iron. Molecules with anti-aggregational and/or antioxidant properties may therefore be potential therapeutic agents.

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Characterization of Tamm-Horsfall Urinary Glycoprotein

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010007254x ◽

1973 ◽

Vol 31 ◽

pp. 420-421

Author(s):

John P. Robinson ◽

J. David Puett

Keyword(s):

Electron Microscopy ◽

Circular Dichroism ◽

Secondary Structure ◽

Quaternary Structure ◽

Normal Adult ◽

Morphological Properties ◽

Adult Males ◽

Circular Dichroïsm ◽

Urinary Glycoprotein

Much work has been reported on the chemical, physical and morphological properties of urinary Tamm-Horsfall glycoprotein (THG). Although it was once reported that cystic fibrotic (CF) individuals had a defective THG, more recent data indicate that THG and CF-THG are similar if not identical.No studies on the conformational aspects have been reported on this glycoprotein using circular dichroism (CD). We examined the secondary structure of THG and derivatives under various conditions and have correlated these results with quaternary structure using electron microscopy.THG was prepared from normal adult males and CF-THG from a 16-year old CF female by the method of Tamm and Horsfall. CF female by the method of Tamm and Horsfall.

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