...Samuel Strader; Andrew B. West The accumulation of aggregated α-synuclein in susceptible neurons in the brain, together with robust activation of nearby myeloid cells, are pathological hallmarks of Parkinson's disease (PD). While microglia represent the dominant type of myeloid cell in the brain...

... tremor, as well as mood and sleep disorders. The pathology of PD has been observed to spread through the central nervous system resulting in progressive brain degeneration and a poor prognosis. Aggregated forms of the protein α-synuclein, particularly intermediary aggregates, referred to as oligomers...

...Thomas Briston; Amy R. Hicks Neurodegenerative proteinopathies are a group of pathologically similar, progressive disorders of the nervous system, characterised by structural alterations within and toxic misfolding of susceptible proteins. Oligomerisation of Aβ, tau, α-synuclein and TDP-43 leads...

... features including the involvement of mitochondria in the mechanism of pathology and misfolding and the accumulation of abnormally aggregated proteins. Neurotoxicity of aggregated β-amyloid, tau, α-synuclein and huntingtin is linked to the effects of these proteins on mitochondria. All these misfolded...

... is expressed in oligodendrocytes and plays a crucial role in the formation of projections in the course of differentiation required for axon ensheathment. Under pathological conditions, TPPP/p25 interacts with α-synuclein, an aberrant protein–protein interaction resulting in aggregation leading...

... to bridge this relationship, focusing on the molecular link between two proteins, α-synuclein and glucocerebrosidase, involved in PD and GD respectively. 1 To whom correspondence should be addressed (email leej4@mail.nih.gov ). 23 7 2013 © The Authors Journal compilation © 2013...

... and IDPs. The present article summarizes findings from experimental and computational studies of the mechanisms of interaction between small molecules and three IDPs in their disordered states: c-Myc, Aβ (amyloid β-peptide) and α-synuclein. 1 To whom correspondence should be addressed (email...

...Andres Binolfi; Francois-Xavier Theillet; Philipp Selenko The notion that human α-synuclein is an intrinsically disordered monomeric protein was recently challenged by a postulated α-helical tetramer as the physiologically relevant protein structure. The fact that this alleged conformation had...

... of the elderly population worldwide. One of the major hallmarks of PD is the occurrence of intracellular protein deposits in the dying neurons, termed Lewy bodies, which contain different proteins, including aggregated α-synuclein and its interacting protein synphilin-1. During the last decade, a number...

... results of recent studies investigating PD (Parkinson's disease) and tauopathies using BAC-transgenic mice carrying either the LRRK2 (leucine-rich repeat kinase 2), α-synuclein ( SNCA ) or MAPT (microtubule-associated protein tau) genes. In all lines, expression of the WT (wild-type) gene resulted...

...Hozefa Amijee; Jill Madine; David A. Middleton; Andrew J. Doig The aggregation of numerous peptides or proteins has been linked to the onset of disease, including Aβ (amyloid β-peptide) in AD (Alzheimer's disease), asyn (α-synuclein) in Parkinson's disease and amylin in Type 2 diabetes. Diverse...

...J. Madine; A.J. Doig; A. Kitmitto; D.A. Middleton The deposition of α-syn (α-synuclein) fibrils in Lewy bodies is a characteristic feature of individuals with neurodegenerative disorders. A peptide comprising the central residues 71–82 of α-syn [α-syn(71–82)] is capable of forming β-sheet-rich...

...K.E. Paleologou; G.B. Irvine; O.M.A. El-Agnaf There is strong evidence for the involvement of α-synuclein in the pathologies of several neurodegenerative disorders, including PD (Parkinson's disease). Development of disease appears to be linked to processes that increase the rate at which α...

...G. Gibson; O.M.A. El-Agnaf; Z. Anwar; C. Sidera; A. Isbister; B.M. Austen A number of human neurodegenerative diseases involve aggregated amyloid proteins in the brain, e.g. Alzheimer's disease (β-amyloid) and Parkinson's disease (α-synuclein). Other examples are rare familial dementias which...

...J. Hardy Loci underlying autosomal dominant forms of most neurodegenerative disease have been identified: prion mutations cause Gerstmann Straussler syndrome and hereditary Creutzfeldt–Jakob disease, tau mutations cause autosomal dominant frontal temporal dementia and α-synuclein mutations cause...

...J. Madine; A.J. Doig; D.A. Middleton α-Synuclein is a 140 amino acid protein, which is associated with presynaptic membranes in the brain, and is the major component of protein aggregates produced during the progression of many neurodegenerative diseases. It has been shown that a central...