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.
Neurodegeneration Unit, Department of Surgery, St. George's Hospital Medical School, Cranmer Terrace, Tooting, London, SW17 0RE, United Kingdom.
O M
OM
El-Agnaf
G B
GB
Irvine
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