A new model for fatty acid hydroxylase-associated neurodegeneration reveals mitochondrial and autophagy abnormalities.

Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a rare disease that exhibits brain modifications and motor dysfunctions in early childhood. The condition is caused by a homozygous or compound heterozygous mutation in (), whose encoded protein synthesizes 2-hydroxysphingolipids and 2-hydroxyglycosphingolipids and is therefore involved in sphingolipid metabolism. A few FAHN model organisms have already been established and give the first insight into symptomatic effects.

Neurodegenerative Disorders: Spotlight on Sphingolipids.

Neurodegenerative diseases are incurable diseases of the nervous system that lead to a progressive loss of brain areas and neuronal subtypes, which is associated with an increase in symptoms that can be linked to the affected brain areas. The key findings that appear in many neurodegenerative diseases are deposits of proteins and the damage of mitochondria, which mainly affect energy production and mitophagy. Several causative gene mutations have been identified in various neurodegenerative diseases; however, a large proportion are considered sporadic.

Ceramide accumulation induces mitophagy and impairs β-oxidation in PINK1 deficiency.

Energy production via the mitochondrial electron transport chain (ETC) and mitophagy are two important processes affected in Parkinson's disease (PD). Interestingly, PINK1, mutations of which cause early-onset PD, plays a key role in both processes, suggesting that these two mechanisms are connected. However, the converging link of both pathways currently remains enigmatic.