Particularly, enhanced p38 activation has been reported in motoneurons from transgenic mice expressing ALS-linked SOD1 mutants [55], [56], [57] as well as in human ALS patients [54].
For example, mice expressing disease-linked variants of TDP43 show abnormal metabolism of a number of metals, although iron appears to be normal (Dang et al., 2014).
We demonstrated that messenger RNA (mRNA) oxidation is a common feature in amyotrophic lateral sclerosis (ALS) patients as well as in many different transgenic mice expressing familial ALS-linked mutant copper-zinc superoxide dismutase (SOD1).
Here we describe the behavioural and pathological features of a line of transgenic mice expressing the ALS-linked mutant TDP-43Q331K.
Heterozygous mice expressing the disease-linked form of CUL3 show increased signalling through the WNK kinase pathway, high blood pressure and a pattern of deranged electrolytes that is typical of human subjects with PHA2E.
Transgenic mice expressing CMT type 1C-linked human SIMPLE mutant develop a late-onset motor and sensory neuropathy associated with abnormal myelin infolding, paranodal defects, and altered nodal organization (Lee et al., 2013).
Thus SOD1 knock-out mice do not show any ALS symptoms, whereas transgenic mice, expressing, for example, the fALS associated mutant G93A human SOD1, develop the symptoms, despite expression of endogenous mouse SOD1 [5], [5].
As induction of autophagy by CysC also protects neurons against various stresses other than SOD1-mediated toxicity and rapamycin protected neurons in mice expressing TAR DNA binding protein 43 (TDP-43), another disease-linked protein accumulated in sporadic ALS and frontotemporal lobar degeneration, CysC treatment may also be useful for SOD1-unrelated ALS as well as the SOD1-linked one.
A significant increase of 3NT was reported in spinal cord of transgenic mice expressing mutated SOD1 (4) and in autopsied spinal cord of FALS patients with genetic mutation of SOD1 and sporadic ALS (SALS) patients (5).
Meanwhile transgenic mice expressing the SOD1L126delTT could be an ideal model for analyzing the disease process of FALS as the SOD1L126delTT protein is inherently monomeric.
