Advances and challenges in understanding the multifaceted pathogenesis of amyotrophic lateral sclerosis.

1. Swiss Med Wkly. 2015 Jan 30;145:w14054. doi: 10.4414/smw.2015.14054. eCollection
2015.

Advances and challenges in understanding the multifaceted pathogenesis of
amyotrophic lateral sclerosis.

Laferriere F(1), Polymenidou M(1).

Author information:
(1)Institute of Molecular Life Sciences, University of Zurich, Switzerland.

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease,
which primarily affects motor neurons leading to progressive paralysis and death
within a few years from onset. The pathological hallmark of ALS is the presence
of cytoplasmic ubiquitinated protein inclusions in motor neurons and glial cells
primarily in the spinal cord. While the vast majority of ALS occurs sporadically
(sALS), in ~10% of cases, called familial ALS (fALS), there is clear indication
of genetic inheritance. In the last decade, enormous progress was made in
unravelling the aetiology of the disease, with the identification of ALS-causing
mutations in new genes, as well as key molecular players involved in the origin
or progression of ALS. However, much more needs to be done, as the pathogenic
mechanisms triggered by a genetic or sporadic event leading to cytotoxicity and
neuronal cell death are still poorly understood. The recent discoveries offer new
possibilities for devising experimental animal and cellular models, which will
hopefully contribute to the development of new techniques for early diagnosis and
the identification of therapeutic targets for ALS. Here we review the current
understanding of the aetiology, genetics, and pathogenic factors and mechanisms
of ALS. We also discuss the challenges in deciphering ALS pathogenesis that
result from the high complexity and heterogeneity of the disease.

DOI: 10.4414/smw.2015.14054
PMID: 25635517 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus