Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by the gradual degeneration
and death of upper and lower motor neurons. Despite continue efforts, the etiology and pathogenesis of
ALS are not well understood yet. The lack of knowledge about molecular and cellular players involved
in the neurodegenerative progression of ALS hinders effective therapy development. Several genomicbased
studies have been conducted to identify genetic contributors to sporadic ALS (SALS) and new
potential pharmacological targets, but these have resulted in short and non-overlapping lists of candidates.
In the last few years, our research group has developed the largest whole-genome expression profile database of
SALS human samples. We have identified several genes deregulated in the motor cortex of SALS patients and analyzed
the role of these genes within deregulated pathways, providing a full molecular portrait of ALS pathogenesis. Some of
deregulated genes encode for proteins that are direct or indirect targets of experimental or therapeutic drugs already applied
to unrelated diseases. In this review, we focus on the potential role of candidate targets in ALS pathophysiology,
highlighting their possible contribution to ALS therapy. The rational selection of the most promising drug targets and related
modulatory drugs may provide a starting point for their preclinical or clinical validation and, hopefully, the development
of more effective treatments for ALS patients.
Keywords: ALS, drug, pharmacology, pathway, target.
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