Review article

NEW FACTS ON THE ETIOPATHOGENESIS OF AMYOTROPHIC LATERAL SCLEROSIS

Paola Riosa

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of motor neurons in the spinal cord, brain stem and the motoric cortex. The etiopathogenesis of amyotrophic lateral sclerosis is still unknown. There are a large number of mechanisms on cell level that could cause a degeneration of motor neurons. In some 5-10% of cases the disease appears in families. Genetic research found that a mutation of the SOD1 gene located on the 21st chromosome accounts for approximately 20% of the ALS cases occurring in families. The research concentrate on the identification of new genetic mutations, so that numerous new gens were discovered in the last years connected to the degeneration of motor neurons. In approximately 90% of cases the disease occurs sporadically, i.e. there is no information on ALS cases within the family. The gene hypothesis does not explain such cases, and scientists believe that the risk of developing the disease includes
a combination of various genetic and environmental risk factors. It must be stressed that a lower Cu/ZnSOD1 enzymatic activity in both the family related and the sporadic cases was noticed, showing cell damage through free radicals and points out the role of oxidative stress in both forms of the disease. Still, genetic factors are not the only reason for the occurrence of the disease. The assumption that ALS is caused by an excitotoxic injury with glutamate has also been confirmed for both form of the disease. The explanation is that the selective degeneration of motor neurons is caused by a higher sensibility of motor neurons to glutamate and the excitotoxic process. A direct connection between exogene neurotoxins and the appearance of the disease has still not been proved; a possible explanation could be that these factors can increase the risk of disease development through a cumulative effect, making the cells more sensitive to degeneration. A smaller number of research indicates disorders in immunological function as the cause of the disease. However, there are still no exact proofs of the immunological hypothesis. The support of neurothrophic factors in the development of motor neurons is being intensively researched. The research itself and the identification of causal and risk factors for the occurrence of both forms of the disease are difficult due to the relative rare occurrence of the disease and the lack of DNA samples of the patients and their family members. There has still been a positive development in the research in the last years due to the creation of DNA banks with national
databases for ALS.

Keywords

motor neuron disease; etiopathogenesis

Hrčak ID:

32110

URI

https://hrcak.srce.hr/32110

Publication date:

22.12.2008.

Article data in other languages: croatian

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