Amyloid pores in mitochondrial membranes

Abstract

Neurodegenerative diseases of the amyloid type include common conditions such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. Despite the fact that the phenotypes of these neuropathic maladies differ widely, ranging from cognitive to motor and psychotic disturbances, they are all characterized by the pathological accumulation and deposition in the central nervous system of well-ordered protein aggregates known as amyloid fibrils. Accumulating evidence indicates that rather than the end-stage mature fibrils, however, it is the smaller, metastable intermediate forms (known as oligomers) of the aggregated protein and peptides which represent the most neurotoxic species (Chiti and Dobson, 2017). One suggested mechanism for such toxicity appears to involve the ability of oligomers to interact with plasma membranes whilst inducing cell leakage (Surguchov et al., 2017). However, contemporary work increasingly points to mitochondria, and hence mitochondrial membranes, as preferential targets for the pathogenic action of oligomers in the neuronal cell (Ghio et al., 2016).