Table 1 |.

Human diseases associated with the Wallerian degeneration pathway

Human disease	Findings	Comment	Refs
Alzheimer disease	NMNAT2 protein and mRNA are reduced in brains of individuals with Alzheimer disease	This finding suggests that reduced NMNAT2 is associated with, and may be a risk factor for, the development of Alzheimer disease	95
Erythromelalgia and peripheral neuropathy	A homozygous NMNAT2 partial loss-of-function mutation in two individuals with erythromelalgia and peripheral neuropathy	Loss-of-function mutation in NMNAT2 results in development of peripheral neuropathy	89
Fetal akinesia deformation syndrome	Compound heterozygous NMNAT2 severe loss-of-function mutations in two fetuses with fetal akinesia deformation syndrome	Severe loss-of-function mutation in NMNAT2 results in stillbirth, mimicking observations in NMNAT2 null mice	90
ALS	GWAS show association of the SARM1 locus with ALS	A pathogenic role of SARM1 in ALS must involve gain-of-function variants that increase the risk of axonal degeneration	101,102
ALS	An ALS-causing mutation in TARDBP reduces levels of stathmin 2 in iPSC-derived motor neurons; a similar decrease is common in sporadic ALS	Low levels of stathmin 2 increase the likelihood of Wallerian degeneration and could therefore be an important modifier or risk factor for ALS	96,97

ALS, amyotrophic lateral sclerosis; GWAS, genome-wide association studies; iPSC, induced pluripotent stem cell; NMNAT2, nicotinamide mononucleotide adenylyltransferase 2; SARM1, sterile-α and Toll/interleukin 1 receptor (TIR) motif containing protein 1; TDP43, transactive response DNA binding protein 43 kDa.