Autophagic pathology and calcium deregulation in neurodegeneration

Abstract

Over the last decades, substantial efforts have been made towards understanding the key players underlying neurodegeneration. However, despite extensive research efforts, the exact molecular mechanism(s) remain unclear, and much less is certain about possible common target(s) amongst distinct age-dependent neurodegenerative disorders. Whilst the precise mechanism(s) underlying neurodegeneration amongst the different diseases remain to be determined, a number of cellular processes have been suggested to be involved in all of them, including protein accumulation and aggregation, oxidative stress, mitochondrial deficits, Ca2+ dyshomeostasis and impairments in lysosomal degradation pathways including macroautophagy. The various possible pathogenic factors are not mutually exclusive, and the aim of much current research is to elucidate the correlation between them to establish successful strategies in limiting the disease process. Here, we summarize recent data that pinpoint Ca2+ dyshomeostasis as a key player underlying neurodegeneration in the context of macroautophagy deregulation. We will provide a brief overview of recent work towards addressing how macroautophagy and Ca2+ deregulation may cause cellular dysfunction linked to the pathogenesis of several neurodegenerative disorders, with emphasis on Parkinson’s disease (PD).