Disease Basis

The cause of sporadic ALS is unknown but it is generally accepted that susceptibility to disease is based upon genetic risk factors and environmental exposure. The disease represents a heterogeneous set of disorders caused by different initiating factors that manifest in a common event, i.e., motor neuron loss. Included among the genetic risk factors for sporadic disease are mutations or polymorphisms in the genes for dynactin (DCTN1, p150 subunit),89 peripherin (PRPH),90 neurofilament heavy chain (NF-H),91 glutamate transporter-2 (EAAT-2), and vascular endothelial growth factor (VEGF).92 Mutations in VEGF have also been associated with multiple neurodegenerative diseases. Familial disease dominantly inherited falls into two classes: disease associated with superoxide dismutase-1 (SOD-1) mutations, for which over 90 are documented, and disease not associated with SOD-1 mutations. For dominantly inherited fALS not associated with SOD-1 mutations, linkages have been made on chromosomes 16, 18, and 20.93 Juvenile fALS forms also exist. For these, genes within chromosomal locations 15q15-22 and 2q33 are linked and inherited in a recessive manner. Although the identity of the gene on chromosome 15 is yet to be determined, ALS2 is the gene localized to chromosome 2. ALS2 encodes a protein of 184 kDa (alsin) that contains three putative guanine-nucleotide exchange factor domains. Alsin is suspected to be involved in protein trafficking since it acts, at least in vitro, as an exchange factor for Rab5a, which is known to be involved in endosome function.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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