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Reduction of glyceraldehyde‐3‐phosphate dehydrogenase activity in Alzheimer's disease and in Huntington's disease fibroblasts
Author(s) -
Mazzola Jennifer L.,
Sirover Michael A.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00033.x
Subject(s) - glyceraldehyde 3 phosphate dehydrogenase , huntington's disease , biology , glycolysis , huntingtin , huntingtin protein , neurodegeneration , microbiology and biotechnology , alzheimer's disease , dehydrogenase , subcellular localization , biochemistry , disease , enzyme , gene , medicine , mutant
New functions have been identified for glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) including its role in neurodegenerative disease and in apoptosis. GAPDH binds specifically to proteins implicated in the pathogenesis of a variety of neurodegenerative disorders including the β‐amyloid precursor protein and the huntingtin protein. However, the pathophysiological significance of such interactions is unknown. In accordance with published data, our initial results indicated there was no measurable difference in GAPDH glycolytic activity in crude whole‐cell sonicates of Alzheimer's and Huntington's disease fibroblasts. However, subcellular‐specific GAPDH–protein interactions resulting in diminution of GAPDH glycolytic activity may be disrupted or masked in whole‐cell preparations. For that reason, we examined GAPDH glycolytic activity as well as GAPDH–protein distribution as a function of its subcellular localization in 12 separate cell strains. We now report evidence of an impairment of GAPDH glycolytic function in Alzheimer's and Huntington's disease subcellular fractions despite unchanged gene expression. In the postnuclear fraction, GAPDH was 27% less glycolytically active in Alzheimer's cells as compared with age‐matched controls. In the nuclear fraction, deficits of 27% and 33% in GAPDH function were observed in Alzheimer's and Huntington's disease, respectively. This evidence supports a functional role for GAPDH in neurodegenerative diseases. The possibility is considered that GAPDH : neuronal protein interaction may affect its functional diversity including energy production and as well as its role in apoptosis.