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This work and the authors' experiments cited were supported by Dirección General del Personal Académico, Universidad Nacional Autónoma de México, (project IN215610) and Consejo Nacional de Ciencia y Tecnología (CONACYT), México (project 128229). L.D.S.C. and U.N.R.J. are recipients of a scholarship from CONACYT.

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**9** 

*1,3USA 2Russia* 

**Role of Neuronal Mitochondrial Metabolic** 

*3Laboratory of Brain Biomarkers, WellStar College of Health & Human Services,* 

Amyotrophic lateral sclerosis (ALS) is one of the group of diseases of the central nerve system (CNS), which are characterized by progressive loss of structure and function of neurons in different regions of brain or spinal cord. Therefore, these diseases are collectively designated as "Neurodegenerative Diseases" (NDDs). Usually the loss of specific functions precedes the death of affected neurons, and the related clinical features depend on localization and degree of neurodegeneration. NDDs include such diseases as Alzheimer's, Parkinson's, Huntington's, spinocerebellar ataxias, and ALS. In spite of differences in predominant localization of neurodegeneration and clinical features, there are many parallels among different neurodegenerative disorders. These include involvement of mitochondrial dysfunctions, increased oxidative stress, and atypical protein assemblies

Amyotrophic lateral sclerosis (ALS) refers to several adult-onset conditions characterized by progressive degeneration of motor neurons. "Amyotrophic" refers to the muscle atrophy, weakness, and fasciculation (spontaneous contraction affecting a small number of muscle fibers) that signify disease of the lower motor neurons. There are two forms of this fatal disease: sporadic, with no known genetic component, and familial, which make up about 10% of all ALS cases (Rowland & Schneider, 2001; Martin et al., 2009). Among the familial cases, approximately 20% are caused by dominantly inherited mutations in the Cu/Zn superoxide dismutase (*SOD1*) gene, with more than 100 known mutations (reviewed in Bruijn et al., 2004). So far, there is very little information that links familial and sporadic cases of the disease. One established fact, based on studies of patients and transgenic animals, is that mitochondria dysfunction is an early manifestation. However, it is unclear whether mitochondrial dysfunctions are the primary pathogenic mechanism, or the result of

Although the cases associated with mutations in the *SOD1* gene comprise only about 2% of all ALS cases, understandably, transgenic animals bearing mutated *SOD1* gene

**1. Introduction** 

(Backman et al., 2006).

some other proximate pathogenic mechanism.

**Phenotype in Pathogenesis of ALS** 

Svetlana Dambinova3 and Herbert L. Bonkovsky1

*2Institute of Molecular Biology and Biophysics, Novosibirsk,* 

*Kennesaw State University, Kennesaw, GA,* 

Alexander Panov1, 3, Nury Steuerwald1, Valentin Vavilin2,

*1Cannon Research Center, Carolinas Medical Center, Charlotte, NC,* 

