A century-old debate on protein aggregation and neurodegeneration enters the clinic

Abstract

The correlation between neurodegenerative disease and protein aggregation in the brain has long been recognized, but a causal relationship has not been unequivocally established, in part because a discrete pathogenic aggregate has not been identified. The complexity of these diseases and the dynamic nature of protein aggregation mean that, despite progress towards understanding aggregation, its relationship to disease is difficult to determine in the laboratory. Nevertheless, drug candidates that inhibit aggregation are now being tested in the clinic. These have the potential to slow the progression of Alzheimer's disease, Parkinson's disease and related disorders and could, if administered presymptomatically, drastically reduce the incidence of these diseases. The clinical trials could also settle the century-old debate about causality.

Detection of protein aggregation with a Bloch surface wave based sensor

“…Hence the early dynamic events in the aggregation process are of high interest [13]. The ability to detect and understand these events is of prime importance to tackle many degenerative diseases, which need to be diagnosed prior to the onset of clinical symptoms [14,15].…”

Imaging of neuroinflammation

“…Formation of intracellular inclusion bodies resulting from aberrant protein folding, abnormal protein-protein interactions and/or dysregulation of the ubiquitin-proteasome system (UPS) are thought to play a principal role in neuronal dysfunction and death of neurons that characterizes several common neurodegenerative diseases [3].…”

Glucocerebrosidase, a new player changing the old rules in Lewy body diseases

“…α -Synuclein binds lipids, such as those in the plasma membrane and synaptic vesicles (Auluck et al , 2010 ). Under pathological conditions, α -synuclein aggregates to form insoluble amyloid fibrils via various forms of oligomeric intermediates (Lansbury and Lashuel , 2006 ). Binding of α -synuclein to lipids seems to modulate its tendency to produce these aggregates (Perrin et al , 2000 ).…”