Table I.

Summary of LSDs with signs of dying-back pathology

Disease	Substrate	Gene	Neuronal defects	Model	Reference
Krabbe’s disease	galactosylsphingosine	galactosylceramidase	Axonal spheroids, loss of axonal calibre, structural and molecular defects in neuromuscular junctions, defects in membrane dynamics and accumulation of α-synuclein	Twitcher mouse	(Cantuti-Castelvetri et al. 2015; Cantuti-Castelvetri et al. 2012; Cantuti Castelvetri et al. 2013; Castelvetri et al. 2011; Smith et al. 2011 Teixeira et al. 2014 White et al. 2009)
Pompe’s disease	glycogen	acid-alpha glucosidase	Enlargement and fragmentation of the endplate. Aberrant levels of neurofilament and change in axonal diameter	acid-alpha glucosidase−/− mouse	(Falk et al. 2015)
Niemann-Pick type C disease	cholesterol	NPC1	Degeneration of neuronal terminals, axonal spheroids filled with synaptic markers, defects in recycling of synaptic vesicles	NPC1 −/− mouse	(Ong et al. 2001; Pressey et al. 2012; Xu et al. 2010)
Niemann-Pick type A disease	sphingomyelin	Acid sphingomyelinase	Axonal spheroids, loss of dendrites and defects in vesicular traffic	ASM −/− mouse and ASM −/− neurons	(Galvan et al. 2008; Kuemmel et al. 1997; Sarna et al. 2001)
Mucopolysaccharidosis III type B	heparan sulfate	α-N-acetylglucosa minidase	Accumulation of α-synuclein, ubiquitin and phosphorylated tau in the cell body, axons and dendrites. Axonal dystrophy	Human post-mortem tissue, NAGLU−/− mouse	(Hamano et al. 2008; Ohmi et al. 2009; Ohmi et al. 2011; Wilkinson et al. 2012)
Neuronal ceroid lipofuscinoses	autofluorescent pigments	palmitoyl protein thioesterase (PPT1), CLN6, or cathepsin D (CLN10)	Axonal spheroids and decrease in the pool of synaptic vesicles. Decrease in the levels of synaptic proteins	PPT1−/−, CLN6−/− or CLN10−/− mice	(Kielar et al. 2009; Partanen et al. 2008; Virmani et al. 2005)
Metachromatic leukodystrophy	sulfatides	arylsulfatase A	Axonal degeneration and accumulation of axoplasmic densities	ARSA−/− mice overexpressor of either UDP-galactoseceramide galactosyltransferase (CGT) or cerebroside sulfotransferase (CST)	(Eckhardt et al. 2007)
Gaucher’s disease	glucocerebroside and glucosylsphingosine	β-d-glucosyl-N- acylsphingosine glucohydrolase	Accumulation of α-synuclein. Decrease in striatal post-synaptic density size. Decrease in action potential amplitudes. Neurotoxic effect of glucosylsphingosine	Inhibition of GBA with conduritol-β-epoxide (CBE). Induced pluripotent stem cells derived neurons from patients	(Ginns et al. 2014; Schueler et al. 2003; Sun et al. 2015)