Amyotrophic lateral sclerosis mutations

Interest in superoxide dismutase has increased in recent years with the discovery that a mutation in the gene coding for SOD is linked to certain types of the neurodegenerative disease amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig s disease. Exactly how mutant forms of SOD are involved in ALS is a subject of intense research. 

The lack of zinc can also be a problem in biological systems and is responsible for disease states. For example, nitric oxide-dependent apoptosis can be induced in motor neurons by zinc-deficient SOD, and in some cases of amyotrophic lateral sclerosis, zinc-deficient SOD may participate in this type of oxidative mechanism involving nitric oxide.969 One form of hereditary human hair loss or alopecia was mapped to a specific gene and a mutation found in affected individuals. The gene encodes a single zinc finger transcription factor protein with restricted expression in the brain and skin.970 Zinc has been implicated in Alzheimer s via beta amyloid formation, and a role has been attributed for the cerebral zinc metabolism in the neuropathogenesis of Alzheimer s disease.971... 

Familial amyotrophic lateral sclerosis. Familial amyotrophic lateral sclerosis (FALS) is observed in =10% of all cases, but substantially more ALS cases are suspected to be influenced to some degree by genetic factors [75], Mutations in two genes (SOD1 and ALS2 Table 39-3) have been shown to cause FALS, apart from mutations in tau (MAPT) leading to FTD with parkinsonism and... 

Rosen, D. R., Siddique, T., Patterson, D. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362 59-62, 1993. 

Andersen,P.M.,Nilsson,P.,Ala-Hurula,V. et al.Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat. Genet. 10 61-66,1995. 

Hadano, S., Hand, C. K., Osuga, H. et al. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat. Genet. 29 166-173, 2001. 

Amyotrophic lateral sclerosis 2 is linked to mutant alsin. In several families with autosomal recessive juvenile ALS, mutations have been identified in ALS2 (chromosome 2), encoding alsin [65, 66], This illness, which was originally described in a Tunisian kindred, is characterized by spasticity (involvement of upper motor neurons) and weakness/amyotrophy (involvement of lower... 

Borchelt, D. R., Lee, M. K., Slunt, H. H. et al. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc. Natl Acad. Sci. U.S.A. 91 8292-8296,1994. 

Pasinelli, P., Borchelt, D. R., Houseweart, M. K., Cleveland, D. W. and Brown, R. H. Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. Neurobiology 95 15763-15768,1998. 

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurones. In 15-25% of cases, the genetic cause of the disease is a mutation of the enzyme Cu+/Zn2+... 

Frontotemporal dementia involves an early and primary degenerative process of frontal and/or temporal cortex. Several disorders fall under this rubric, such as Pick s disease and the dementia associated with amyotrophic lateral sclerosis (ALS). ALS is a degenerative disease of upper motor neurons that is sometimes accompanied by a frontal lobe dementia (Vercelletto et al. 1999 Abe et al. 1997). ALS has been associated with mutations in the free radical scavenging enzyme superoxide dismutase 1 (Price et al. 1997). Pick s disease is associated histologically with a loss of neurons and cytoplasmic Pick bodies in surviving neurons. 

Genetic mutations in Cu—Zn SOD have been linked to the neurodegenera-tive disease amyotrophic lateral sclerosis (ALS), Lou Gehrig s disease [89],... 

Morrison, B. M., and Morrison, J. H. (1999). Amyotrophic lateral sclerosis associated with mutations in superoxide dismutase A putative mechanism of degeneration. Brain Res. Rev. 29, 121—135. 

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