AUTHOR=Edens Brittany M. , Miller Nimrod , Ma Yong-Chao 

TITLE=Impaired Autophagy and Defective Mitochondrial Function: Converging Paths on the Road to Motor Neuron Degeneration

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=10

YEAR=2016

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2016.00044

DOI=10.3389/fncel.2016.00044

ISSN=1662-5102

ABSTRACT=<p>Selective motor neuron degeneration is a hallmark of amyotrophic lateral sclerosis (ALS). Around 10% of all cases present as familial ALS (FALS), while sporadic ALS (SALS) accounts for the remaining 90%. Diverse genetic mutations leading to FALS have been identified, but the underlying causes of SALS remain largely unknown. Despite the heterogeneous and incompletely understood etiology, different types of ALS exhibit overlapping pathology and common phenotypes, including protein aggregation and mitochondrial deficiencies. Here, we review the current understanding of mechanisms leading to motor neuron degeneration in ALS as they pertain to disrupted cellular clearance pathways, ATP biogenesis, calcium buffering and mitochondrial dynamics. Through focusing on impaired autophagic and mitochondrial functions, we highlight how the convergence of diverse cellular processes and pathways contributes to common pathology in motor neuron degeneration.</p>