Review: formation and properties of amyloid-like fibrils derived from alpha-synuclein and related proteins.
Synucleinsare small proteins that are highly expressed in brain tissue and are localised at presynaptic terminals in neurons. alpha-Synuclein has been identified as a component of intracellular fibrillar protein deposits in several neurodegenerative diseases, and two mutant forms of alpha-synuclein have been associated with autosomal-dominant Parkinson's Disease. A fragment of alpha-synuclein has also been identified as the non-Abeta component of Alzheimer's Disease amyloid. In this review we describe some structural properties of alpha-synuclein and the two mutant forms, as well as alpha-synuclein fragments, with particular emphasis on their ability to form beta-sheet on ageing and aggregate to form amyloid-like fibrils. Differences in the rates of aggregation and morphologies of the fibrils formed by alpha-synuclein and the two mutant proteins are highlighted. Interactions between alpha-synuclein and other proteins, especially those that are components of amyloid or Lewy bodies, are considered. The toxicity of alpha-synuclein and related peptides towards neurons is also discussing in relation to the aetiology of neurodegenerative diseases.
El-Agnaf
O M
OM
Neurodegeneration Unit, Department of Surgery, St. George's Hospital Medical School, Cranmer Terrace, Tooting, London, SW17 0RE, United Kingdom.
Irvine
G B
GB
D000682:Amyloid; D001483:Base Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D019636:Neurodegenerative Diseases / Q000378:metabolism; D011487:Protein Conformation; D051843:Synucleins; D051844:alpha-Synuclein
D000682:Amyloid; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein