title: Impaired Autophagy and Defective Mitochondrial Function: Converging Paths on the Road to Motor Neuron Degeneration.
abstract: 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.
authors.affiliation: Departments of Pediatrics, Neurology, and Physiology, Northwestern University Feinberg School of MedicineChicago, IL, USA; Lurie Children's Hospital of ChicagoChicago, IL, USA.
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Edens
authors.affiliation: Departments of Pediatrics, Neurology, and Physiology, Northwestern University Feinberg School of MedicineChicago, IL, USA; Lurie Children's Hospital of ChicagoChicago, IL, USA.
authors.forename: Nimrod
authors.initials: N
authors.lastname: Miller
authors.affiliation: Departments of Pediatrics, Neurology, and Physiology, Northwestern University Feinberg School of MedicineChicago, IL, USA; Lurie Children's Hospital of ChicagoChicago, IL, USA.
authors.forename: Yong-Chao
authors.initials: YC
authors.lastname: Ma
keywords: ALS; ATP biogenesis; autophagy; calcium homeostasis; mitochondria; motor neuron disease; oxidative stress; protein aggregation