In a pilot clinical study that we recently published we found that lithium 
administration slows the progression of Amyotrophic Lateral Sclerosis (ALS) in 
human patients. This clinical study was published in addition with basic (in 
vitro) and pre-clinical (in vivo) data demonstrating a defect of autophagy as a 
final common pathway in the genesis of ALS. In fact, lithium was used as an 
autophagy inducer. In detailing the protective effects of lithium we found for 
the first time that this drug stimulates the biogenesis of mitochondria in the 
central nervous system and, uniquely in the spinal cord, it induces 
neuronogenesis and neuronal differentiation. In particular, the effects induced 
by lithium can be summarized as follows: (i) the removal of altered mitochondria 
and protein aggregates; (ii) the biogenesis of well-structured mitochondria; 
(iii) the suppression of glial proliferation; (iv) the differentiation of newly 
formed neurons in the spinal cord towards a specific phenotype. In this addendum 
we focus on defective autophagy as a "leit motif" in ALS and the old and novel 
features of lithium which bridge autophagy activation to concomitant effects 
that may be useful for the treatment of a variety of neurodegenerative 
disorders. In particular, the biogenesis of mitochondria and the increase of 
calbindin D 28K-positive neurons, which are likely to support powerful 
neuroprotection towards autophagy failure, mitochondriopathy and neuronal loss 
in the spinal cord.