NR ARKV
AU Walsh,D.M.; Selkoe,D.J.
TI Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration.
QU Protein and Peptide Letters 2004 Jun; 11(3): 213-28
PT journal article; review; review, tutorial
AB Extracellular fibrous amyloid deposits or intracellular inclusion bodies containing abnormal protein fibrils characterize many different neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies, multiple system atrophy, Huntington's disease, and the transmissible 'prion' dementias. There is strong evidence from genetic, transgenic mouse and biochemical studies to support the idea that the accumulation of protein aggregates in the brain plays a seminal role in the pathogenesis of these diseases. How monomeric proteins ultimately convert to highly polymeric deposits is unknown. However, studies employing, synthetic, cell-derived and purified recombinant proteins suggest that amyloid proteins first come together to form soluble low n-oligomers. Further association of these oligomers results in higher molecular weight assemblies including so-called 'protofibrils' and 'ADDLs' and these eventually exceed solubility limits until, finally, they are deposited as amyloid fibrils. With particular reference to AD and PD, we review recent evidence that soluble oligomers are the principal pathogenic species that drive neuronal dysfunction.
ZR 139
MH Alzheimer Disease/genetics/*metabolism/pathology; Amyloid beta-Protein/chemistry/genetics/*metabolism; Animals; Brain/*metabolism/pathology; Humans; Nerve Tissue Proteins/chemistry/genetics/*metabolism; Parkinson Disease/genetics/*metabolism/pathology; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Solubility
AD Department of Neurology, Harvard Medical School, Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA. dwalsh@rics.bwh.harvard.edu
SP englisch
PO Niederlande