Recent advances in amyotrophic lateral sclerosis research

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. Despite several genetic breakthroughs, the actual cause and mechanism of neurodegeneration in ALS remains a mystery. Nevertheless, recent scientific and clinical advances have led to the development of new therapeutic strategies for this progressive, fatal disorder. We review the progress of the most recent clinical trials in ALS, taking into account some of the hurdles encountered by these studies. We also discuss the potential role of retroviral infection as a cause or contributor to ALS, which is one of the most recent hypotheses for the pathogenesis of the disease. The genetic background of ALS is summarized and special attention is given to the newly identified ALS gene ALS2, and to those that are currently being investigated. The last part of this review is dedicated to the mutation in superoxide dismutase-1 (SOD1). The hypothesized deleterious mechanisms of mutant SOD1 are discussed, as well as the possibilities that the mutant protein activates the apoptotic cell death process and that these molecular alterations can be exploited to devise experimental neuroprotective therapies.

Effects of estrogen on lifespan and motor functions in female hSOD1 G93A transgenic mice

“…These impairments lead to progressive muscle weakness, atrophy, and respiratory paralysis, with mortality usually occurring within 3-5 years after symptom onset [1][2][3][4]. Sporadic cases with few known genetic components account for ∼90% of ALS diagnoses [5,6], while the remaining ∼10% are known familial ALS (fALS).…”

The Neuroprotective Functions of Selenoprotein M and its Role in Cytosolic Calcium Regulation

“…Oxidative stress is implicated in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease (9,16,32). Selenoproteins with known functions include the glutathione peroxidase family (GPx), thioredoxin reductases (TRxR), and the deiodinases (DIO) (17).…”

Protective effect of valproic acid on cultured motor neurons under glutamate excitotoxic conditions. Ultrastructural study

“…Among various pathogenic factors, oxidative stress, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and proteasomal dysfunction are considered. However, the real cause of the disease, its natural history, classification, mechanism of progression and potential therapeutic targets are still under debate [13,[29][30][31]35,36,41].…”