PMID- 12428732
OWN - NLM
STAT- MEDLINE
DCOM- 20021216
LR  - 20191106
IS  - 0161-813X (Print)
IS  - 0161-813X (Linking)
VI  - 23
IP  - 4-5
DP  - 2002 Oct
TI  - Alteration of intracellular structure and function of glyceraldehyde-3-phosphate 
      dehydrogenase: a common phenotype of neurodegenerative disorders?
PG  - 603-9
AB  - Recent evidence reveals that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is 
      not simply a classical glycolytic protein of little interest. Instead, it is a 
      multifunctional protein with diverse cytoplasmic, membrane and nuclear 
      activities. Significantly, each activity is separate and distinctfrom its role in 
      energy production. Its nuclear activities include its emerging role in apoptosis 
      especially in neuronal cells. GAPDH translocates into the nucleus during 
      programmed cell death. Introduction of antisense GAPDH sequences reduces 
      apoptosis and prevents its nuclear translocation. Independent analyses 
      demonstrate that GAPDH may be involved in the cellular phenotype of age-related 
      neurodegenerative disorders. GAPDH binds uniquely in vitro to the beta-amyloid 
      precursor protein (betaAPP), to huntingtin as well as to other triplet repeat 
      neuronal disorder proteins. In Parkinson's disease (PD) cells, immunofluorescent 
      data suggests the co-l localization of GAPDH and alpha-synuclein in Lewy bodies. 
      Drugs used to treat PD bind specifically to GAPDH. Our recent findings (Mazzola 
      and Sirover, 2001) demonstrate a subcellular reduction in GAPDH glycolytic 
      activity in Alzheimer's disease (AD) and in Huntington's disease (HD) cells. The 
      latter may be due to intracellular alteration of GAPDH structure (Mazzola and 
      Sirover 2002). We discuss the hypothesis that the intracellularformation of 
      GAPDH: neuronal protein complexes may represent an emerging cellular phenotype of 
      neurodegenerative disorders. The cytoplasmic binding of neuronal proteins to 
      GAPDH could affect energy production. Nuclear interactions could affect its 
      apoptotic activity. Other functions of this multidimensional protein may also be 
      inhibited. Experimental paradigms to test this hypothesis are considered.
FAU - Mazzola, Jennifer L
AU  - Mazzola JL
AD  - Department of Pharmacology, Temple University School of Medicine, Philadelphia, 
      PA 19140, USA.
FAU - Sirover, Michael A
AU  - Sirover MA
LA  - eng
GR  - AG 14566/AG/NIA NIH HHS/United States
GR  - DA 72370/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/*genetics
MH  - Humans
MH  - Neurodegenerative Diseases/drug therapy/*enzymology/*genetics/pathology
MH  - Phenotype
MH  - Subcellular Fractions/enzymology
MH  - Trinucleotide Repeats
RF  - 63
EDAT- 2002/11/14 04:00
MHDA- 2002/12/18 04:00
CRDT- 2002/11/14 04:00
PHST- 2002/11/14 04:00 [pubmed]
PHST- 2002/12/18 04:00 [medline]
PHST- 2002/11/14 04:00 [entrez]
AID - S0161-813X(02)00062-1 [pii]
AID - 10.1016/s0161-813x(02)00062-1 [doi]
PST - ppublish
SO  - Neurotoxicology. 2002 Oct;23(4-5):603-9. doi: 10.1016/s0161-813x(02)00062-1.